Expression of DNA repair genes in ovarian cancer samples: Biological and clinical considerations

Abstract

The purpose of this study was to investigate retrospectively the mRNA expression of genes involved in different DNA repair pathways implicated in processing platinum-induced damage in 171 chemotherapy-naïve ovarian tumours and correlate the expression of the different genes with clinical parameters. The expression of genes involved in DNA repair pathways (PARP1, ERCC1, XPA, XPF, XPG, BRCA1, FANCA, FANCC, FANCD2, FANCF and PolEta), and in DNA damage transduction (Chk1 and Claspin) was measured by RT-PCR in 13 stage I borderline and 77 stage I and 88 III ovarian carcinomas.  


ERCC1, XPA, XPF and XPG genes were significantly less expressed in stage III than in stage I carcinoma; BRCA1, FANCA, FANCC, FANCD2 gene expressions were low in borderline tumours, higher in stage I carcinomas and lower in stage III samples. High levels of ERCC1, XPA, FANCC, XPG and PolEta correlated with an increase in Overall Survival (OS) and Progression Free Survival (PFS), whilst high BRCA1 levels were associated with PFS on univariate analysis.

With multivariate analyses no genes retained an association when adjusted by stage, grade and residual tumour. A tendency towards a better PFS was observed in patients with the highest level of ERCC1 and BRCA1 after platinum-based therapy than those given both platinum and taxol. The expression of DNA repair genes differed in borderline stage I, stage I and stage III ovarian carcinomas. The role of DNA repair genes in predicting the response in ovarian cancer patients seems far from being established.

blog: Taking a Stab at Cost-Effectiveness | Work In Progress

"....With an aim toward making some small step forward in that direction, Cohn et al tried analyzing the cost-effectiveness of Avastin in the treatment of ovarian cancer. (I know I’ve written about Avastin here before, and I don’t mean to pick on this drug, as if it is the richest child on the fancy pharmaceutical playground. This kind of analysis works well here because the high-priced drug acts almost like a caricature for cost considerations in general.)..."

research: Laboratory News | Reversing migratory cancer cells - miR-428

4th Annual OMG! Cancer Summit For Young Adults NYC Apr 16-17th

Research Advocacy Network: 2010 Survey of Advocates Providing Results to Participants in Biospecimen Studies

Contents
Introduction
Overview of Advocate Survey
Survey Results
Summary and Conclusions

"Introduction
If you provided a biospecimen for research
purposes, would you want to know the
results of your individual tests? Would you
want these results only if they had health
implications? Who would you want to
provide you with these results – your
doctor? A genetic counselor? Someone else?..."

full free access: Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries : The Lancet Oncology

Note: there is also chemotherapy-induced secondary cancers (not part of this study) but putting all treatment-related therapies (adverse events) in perspective
--------------------------------------------------------------------------------------------
Interpretation
A relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors, such as lifestyle or genetics.

Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial : The Lancet Oncology

Background

Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain.
We aimed to establish whether colonic stenting has better health outcomes than does emergency surgery.

Vitamin D and Prevention of Cancer — Ready for Prime Time? — NEJM

"Despite biologic plausibility and widespread enthusiasm, the IOM committee found that the evidence that vitamin D reduces cancer incidence and related mortality was inconsistent and inconclusive as to causality.
New trials assessing moderate-to-high-dose vitamin D supplementation for cancer prevention are in progress and should provide additional information within 5 to 6 years.
Although future research may demonstrate clear benefits of vitamin D related to cancer and other nonskeletal health outcomes, and possibly support higher intake requirements, the existing evidence falls short."

Apr 2011(pdf): Cost-Effectiveness of Genetic Screening for Lynch Syndrome (Available at obgmanagement.com)

Supported by
Myriad Genetics Laboratories, Inc

KEY POINTS

• Lynch syndrome is a hereditary predisposition to
colorectal and endometrial cancers (and other specific
malignancies), resulting from a gene mutation
• Lynch syndrome is the most common heritable cause
of colorectal cancer and endometrial cancer
• Practice guidelines limit risk assessment of Lynch syndrome
to 1) genetic testing in people in whom malignancies
have already developed and 2) mitigation of
the impact of disease by colonoscopic and endometrial
surveillance, and surgical prophylaxis
• No primary screening strategies currently exist for Lynch
syndrome
• Over 50% of women with Lynch syndrome who develop
two primary cancers develop a gynecologic cancer
before colon cancer
• Guidelines issued by ACOG recommend that ObGyns
incorporate identification and management of women
who have hereditary breast and ovarian cancer syndrome
into practice; similar guidelines do not exist for
Lynch syndrome
• A new and powerful study has established evidence for
a protocol of primary screening of Lynch syndrome at a
particular threshold of individual risk
• Specifically, primary screening for unaffected patients,
with risk assessment conducted beginning between
25 and 35 years of age, followed by genetic testing of
people whose risk exceeds 5%, has the potential to improve
health outcomes in a cost-effective way

commentary: re: Lengthened WHI Follow-Up: Postmenopausal Estrogen Therapy - Women's Health

full free access: Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy, April 6, 2011— JAMA

Guiding the guidelines : The Lancet

...Clinical Practice Guidelines We Can Trust is the tandem document from the IOM—tandem in the sense that one of these standards states that a systematic review must precede guideline formulation. The IOM points out that the database of the Guidelines International Network includes more than 3700 guidelines from 39 countries. The standards were formulated to overcome common deficiencies—particularly in bias and how bias is handled—in existing guidelines. These deficiencies include the variable quality of evidence, poorly done systematic reviews, methodology that is not transparent, a development group that does not reflect all stakeholders, and unmanaged conflicts of interest. The IOM recommends that before the development group is formed, conflicts of interest need to be fully disclosed—and their definition includes financial, intellectual, and institutional interests. The prospective panel members should also explain how any conflicts they might have could influence the guideline process. The IOM is clear in some specific areas: members of the group need to divest relevant financial investments they or family members hold, and not take part in advisory boards or marketing activities with relevant companies. Additionally, the chair and co-chairs should have no conflicts of interest, members with conflicts should form a minority, and funders should have no role in guideline development. Overall, tough talk from the IOM—but much needed talk. Apart from expert members in the group, the standards include involvement of patients or their representatives.

video/text: Palliative Medicine: Care versus Cure? Dr Diane Meier/ Richard Heffner's Open Mind - dialogue (U.S.)

AIR DATE: 2/26/2011

High-dose vitamin C: Can it kill cancer cells? - MayoClinic.com

My Sister's Voice (Canada) Lunafest - April 30th

For more information, visit us at lunafest.org

TICKET INFORMATION:
mysistersvoice@rogers.com
PHONE 905.666.3010

update for blog readers - newsreel

Newsreel section:

3 sections are now available for the newsreel section (latest news items)

scroll down to the newsreel section (see right hand side of blog) & then click on: ovarian cancer or BRCA or Lynch Syndrome

Lynch Syndrome Hereditary Cancers Public Awareness Day | Fight Colorectal Cancer

Increased Risk of Cancer

If a parent carries a Lynch mutation there is a 50-50 chance that their child will inherit Lynch syndrome with

• 60 to 80 percent increased lifetime risk of colorectal cancer.
• 40 to 70 percent increased risk of endometrial cancer (cancer of the uterus lining).
• 13 percent increased risk for stomach cancer
• 12 percent increased risk of ovarian cancer.
• smaller, but significant risk of small intestine, urinary tract, heptobiliary (liver, gall bladder and bile ducts), skin, and brain cancers.
• Some families may also have increased risk for breast cancer.

Note: 
Lynch Syndrome is also noted for multiple primary cancers (different cancers in one person)

medical news: Protection Against Cell Damage From Antioxidant Formula Prior To Radiation Exposure

"A unique formulation of antioxidants taken orally before imaging with ionizing radiation minimizes cell damage, noted researchers at the Society of Interventional Radiology's 36th Annual Scientific Meeting in Chicago, Ill. In what the researchers say is the first clinical trial of its kind, as much as a 50 percent reduction in DNA injury was observed after administering the formula prior to CT scans.

"In our initial small study, we found that pre-administering to patients a proprietary antioxidant formulation resulted in a notable dose-dependent reduction in DNA injury," said Kieran J. Murphy, M.D., FSIR, professor and vice chair, director of research and deputy chief of radiology at the University of Toronto and University Health Network, Toronto, Ontario, Canada. "This could play an important role in protecting adults and children who require imaging or a screening study," he added.

"Pre-administering this formula before a medical imaging exam may be one of the most important tools to provide radioprotection and especially important for patients in the getting CT scans," said Murphy. The study's data support the theory about a protective effect during these kinds of exposure, he explained....."cont'd

link to abstract:

"Purpose:  

We examine use of the free radical scavengers vitamin C (VC), glutathione (GL) and uric acid (UA) as a pre-medication strategy prior to radiation exposures typical of medical imaging studies. Our intent was to develop a simple cocktail of antioxidants to be taken orally prior to X-Ray exposures that can protect a patient’s DNA against free radical mediated radiation injury"

link to meeting:

/

JCO -- Collected Resources : Survivorship issues

Note: 19 (hmmmmm...) articles

JCO -- Collected Resources : Chemotherapy - Ovarian Cancer articles

Note: 61 articles

JCO -- Collected Resources : All Art of Oncology Articles

Note: 175 individual articles

from the series: Art in Oncology: How Patients Add Life to Their Days - JCO

>

Why do People get Cancer? « Dr. Robert A. Nagourney – Rational Therapeutics – Blog discusses multiple primaries uterine/colon (Lynch Syndrome)

Note: the article lacks specific drug/chemotherapy intervention information which may be helpful to others

open access journal: Journal of Ovarian Research Differential hRad17 expression by histologic subtype of ovarian cancer

Background
In the search for unique ovarian cancer biomarkers, ovarian specific cDNA microarray analysis identified hRad17, a cell cycle checkpoint protein, as over-expressed in ovarian cancer. The aim of this study was to validate this expression.

Methods
Immunohistochemistry was performed on 72 serous, 19 endometrioid, 10 clear cell, and 6 mucinous ovarian cancers, 9 benign ovarian tumors, and 6 normal ovarian tissue sections using an anti-hRad17 antibody. Western blot analysis and quantitative PCR were performed using cell lysates and total RNA prepared from 17 ovarian cancer cell lines and 6 normal ovarian epithelial cell cultures (HOSE).


Results
Antibody staining confirmed upregulation of hRad17 in 49.5% of ovarian cancer cases. Immunohistochemistry demonstrated that only 42% of serous and 47% of endometrioid subtypes showed overexpression compared to 80% of clear cell and 100% of mucinous cancers.

Conclusions
hRad17 is over-expressed in ovarian cancer. This over-expression varies by subtype suggesting a role in the pathogenesis of these types. Functional studies are needed to determine the potential role of this protein in ovarian cancer.

 PDF

REVIEW ARTICLE Online Open article: Biosimilar agents in oncology/haematology: from approval to practice

Abstract

The regulation of biosimilars is a process that is still developing. In Europe, guidance regarding the approval and use of biosimilars has evolved with the products under consideration. It is now more than 3 years since the first biosimilar agents in oncology support, erythropoiesis-stimulating agents, were approved in the EU. More recently, biosimilar granulocyte colony-stimulating factors have received marketing approval in Europe. This review considers general issues surrounding the introduction of biosimilars and highlights current specific issues pertinent to their use in clinical practice in oncology. Information on marketing approval, extrapolation, labelling, substitution, immunogenicity and traceability of each biosimilar product is important, especially in oncology where patients are treated in repeated therapy courses, often with complicated protocols, and where biosimilars are not used as a unique therapy for replacement of e.g. growth hormone or insulin. While future developments in the regulation of biosimilars will need to address multiple issues, in the interim physicians should remain aware of the inherent differences between biosimilar and innovator products.

Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries : The Lancet Oncology

Blogger's Note: anticancer therapies also infer a risk of secondary cancers - treatment related secondary cancers - to put this in perspective

(U.S.) March 30th 2011 is Lynch Syndrome Hereditary Cancers Public Awareness Day - media

"State leaders, including the Governors of Oregon, Nevada, Arizona, Colorado, Missouri, Louisiana and Alabama, have joined a nationwide public awareness campaign by proclaiming March 30, 2011, Lynch Syndrome Hereditary Cancers Public Awareness Day....cont'd

full free access: Breast and Ovarian Cancer Risk due to Prevalence of BRCA1 and BRCA2 Variants in Pakistani Population: A Pakistani Database Report

Abstract

Pakistani population has a very rich anthrogeneological background with waves of migration from neighboring regions. Incidence rates of breast and ovarian cancer in Pakistan are on such a rapid rise that it is necessary to check the contributory factors, genetic and nongenetic. An insight into the prevalence data emphasizes the formulation of a BRCA1 and BRCA2 database for the Pakistani population.....

Most of BRCA1 and BRCA2 research has been focused on the Caucasian populations; however, the allelic frequency of higher penetrance genes in the Asian population may be higher than that in Caucasian population.................. cont'd (abstract/full free access)

see full paper for further information 

examples: Figure 3 & 4: (brca 1/brca 2/specific mutations/variants):

abstract: DICER1 Mutations in Familial Multinodular Goiter (thyroid) With and Without Ovarian Sertoli-Leydig Cell Tumors

define: 

multinodular goiter - A multinodular goiter is  a thyroid gland that is usually enlarged and contains multiple thyroid nodules.

Pleuropulmonary blastoma (PPB) is a rare cancer originating in the lung or pleural cavity....
en.wikipedia.org/wiki/Pleuropulmonary_blastoma

 

---------------------------------------------------------------------------------------

Objective To determine whether familial MNG  (multinodular goiter) with or without SLCT (Sertoli-Leydig cell tumor of the ovary) in the absence of PPB (pleuropulmonary blastoma)  was associated with mutations in DICER1. 

 

Conclusions DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.

EvidenceUpdates - Interventions for preventing neuropathy caused by cisplatin and related compounds

BACKGROUND:
Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.


AUTHORS' CONCLUSIONS:
At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

EvidenceUpdates: Interventions to enhance return-to-work for cancer patients. Cochrane Database Systematic Rev. 2011

Cancer survivors are 1.4 times more likely to be unemployed than healthy people. It is therefore important to provide cancer patients with programmes to support the return-to-work process.

OBJECTIVES: To evaluate the effectiveness of interventions aimed at enhancing return-to-work in cancer patients.

link - updated Comments from Clinical Raters

just for fun - most popular viewed blog posts this week

audio interview - critical discussion: CBC.ca | Q ...   ASL Video: Ovarian Cancer Information for the Deaf... Recruitment of newly diagnosed ovarian cancer pati... Prognostic Significance of Splenectomy as Part of ... PARP Inhibitor Active in Ovarian Cancer (prelimina...

Doctor and Patient: Interns at the Operating Table - NYTimes.com

included in the article:
This month The Journal of the American College of Surgeons published the results of a study on how well patients come through when a surgeon-in-training is involved in the operation.

(STUDY DESIGN:

We identified 607,683 surgical cases from 234 hospitals from the 2006 to 2009 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Outcomes were compared by resident involvement for all general and vascular cases as well as for specific general surgical procedures.)

Surgeons' and residents' double-gloving practices at 2 teaching hospitals in Ontario (patient safety/injury)

".......Of the 77% who reported at least 1 injury/year, 67% stated that they had not reported it to an employee health service. 

Background: Surgeons and residents are at increased risk of exposure to blood-borne pathogens owing to percutaneous injury (PI) and contamination. One method known to reduce risk is double-gloving (DG) during surgery.
Conclusion: Percutaneous injuries occur frequently during surgery, yet routine DG (double gloved), an effective means of reducing risk, was carried out by less than half of the surgeons and residents participating in this study. This highlights the need for a more concerted and broad-based approach to increase the use of a measure that is effective, inexpensive and easily carried out."

Canadian Journal of Surgery Editorial: The continuing challenge of surgical access

"........Perhaps a wider range of
skills would provide new surgeons with a buffer, helping
them to work within a resource-constrained system. The
idea that “you get to know so much about 1 thing that
pretty soon you know little about everything” haunts surgeons
who limit their skill sets...."

(U.S.) Health Alert: Disease Clusters Spotlight the Need to Protect People from Toxic Chemicals

Note:

1)  search terms of 'ovarian'; 'gynecologic' & 'female reproductive' produced zero results;
2)  states included in report: Arkansas, California, Delaware, Florida, Louisiana, Michigan, Missouri, Montana, North Carolina, Ohio, Pennsylvania, Tennessee, Texas

About NRDC
The Natural Resources Defense Council (NRDC) is an international nonprofit environmental organization with
more than 1.3 million members and online activists.  www.nrdc.org.


Cancer Clusters,
Disease, and the need to Protect
People from Toxic Chemicals
An unusually large number of people sickened by a disease in a certain place and
time is known as a ‘disease cluster’. Clusters of cancer, birth defects, and other
chronic illnesses have sometimes been linked to chemicals or other toxic pollutants
in local communities, although these links can be controversial. There is a need for
better documentation and investigation of disease clusters to identify and address
possible causes. Meanwhile, toxic chemicals should be identified and controlled
through reform of the Toxic Substances Control Act, so these chemicals don’t
pollute communities and sicken people.

full free access: Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas - Journal of Pathology

Abstract

PPP2R1A mutations have recently been described in 3/42 (7%) of clear cell carcinomas of the ovary. ...............This putative tumour suppressor complex is involved in growth and survival pathways. Through targeted sequencing of PPP2R1A, we identified somatic missense mutations in 40.8% (20/49) of high-grade serous endometrial tumours, and 5.0% (3/60) of endometrial endometrioid carcinomas. Mutations were also identified in ovarian tumours at lower frequencies: 12.2% (5/41) of endometrioid and 4.1% (2/49) of clear cell carcinomas. No mutations were found in 50 high-grade and 12 low-grade serous carcinomas. Amino acid residues affected by these mutations are highly conserved across species and are involved in direct interactions with regulatory B-subunits of the PP2A holoenzyme. PPP2R1A mutations in endometrial high-grade serous carcinomas are a frequent and potentially targetable feature of this disease. The finding of frequent PPP2R1A mutations in high-grade serous carcinoma of the endometrium but not in high-grade serous carcinoma of the ovary provides clear genetic evidence that these are distinct diseases

Winter EBulletin 2011 Turning Up the Volume! - newsletter from Ontario Women’s Health Network E-Bulletin

ASL Video: Ovarian Cancer Information for the Deaf and Hearing Impaired

ASL Video: Ovarian Cancer Information for the Deaf and Hearing Impaired

ASL Video: Ovarian Cancer Information for the Deaf and Hearing Impaired (plus transcript)

Introduction

ASL Video and Voice Overlay

Charities Listings (ovarian cancer) Canada - government of Canada website including tax return information

Canada Revenue Agency

www.cra.gc.ca

Institutional links

Basic Search Results

Statistics and data on the Charities and Giving Web pages are compiled by the Charities Directorate of the Canada Revenue Agency (CRA) for the sole purpose of providing the public with direct access to information about charities in Canada.

The CRA is not responsible for the use and manipulation by any persons of this information.
Charity Status: Canadian Registered Charities
Charity Name: ovarian cancer

A search using the information shown above gave this result:
5 matches found.

Charity Name: FONDATION DU CANCER HEREDITAIRE DU SEIN ET DES OVAIRES/HEREDITARY BREAST AND OVARIAN CANCER FOUNDATION / 883465304RR0001

Charity Status: Registered

Effective Date of Status: 2003-10-15

Sanction: N/A

Address: 5791 FERNCROFT ROAD

City: HAMPSTEAD Province/Territory/Other: QUEBEC Country: CA

Postal Code/Zip Code: H3X1C6

Charity Type: Health

Category: Services Other Than Hospitals

Information Return: T3010 Return

Charity Name: HEREDITARY BREAST OVARIAN CANCER SOCIETY OF ALBERTA / 856019336RR0001

Charity Status: Registered

Effective Date of Status: 2005-01-01

Sanction: N/A

Address: 114 11728 KINGSWAY AVE

City: EDMONTON Province/Territory/Other: ALBERTA Country: CA

Postal Code/Zip Code: T5G0X5

Charity Type: Health

Category: Services Other Than Hospitals

Information Return: T3010 Return

Charity Name: Ovarian Cancer Awareness & Treatment in Saskatchewan Corp. / 800916694RR0001

Charity Status: Registered

Effective Date of Status: 2010-01-01

Sanction: N/A

Address: 700-1914 HAMILTON ST

City: REGINA Province/Territory/Other: SASKATCHEWAN Country: CA

Postal Code/Zip Code: S4P3N6

Charity Type: Health

Category: Services Other Than Hospitals

Information Return: T3010 Return

Charity Name: Ovarian Cancer Canada/Cancer de l'Ovaire Canada / 872974845RR0001

Charity Status: Registered

Effective Date of Status: 1998-08-01

Sanction: N/A

Address: 145 FRONT ST EAST SUITE 101

City: TORONTO Province/Territory/Other: ONTARIO Country: CA

Postal Code/Zip Code: M5A1E3

Charity Type: Health

Category: Services Other Than Hospitals

Information Return: T3010 Return
direct link - compensation section 

What was the charity's total expenditure on all compensation in the fiscal period?

$ 1,420,438

Charity Name: THE CAROL ANNIBALE OVARIAN CANCER FOUNDATION / 863136321RR0001

Charity Status: Registered

Effective Date of Status: 2000-08-11

Sanction: N/A

Address: 74 MUZICH PLACE

City: WOOBRIDGE Province/Territory/Other: ONTARIO Country: CA

Postal Code/Zip Code: L4L9C5

Charity Type: Health

Category: Services Other Than Hospitals

Information Return: T3010 Return

Blog: Our Cancer — "It’s NOT Easy to Go There.." Laurie Singer Sievers

"....What about all of us who are carrying around the baggage of the disease? It's real and if you ask me, it's an epidemic."

Treating Depression with Anti-Inflammatory Agents > CMELLC - Life Long Learning > Treating the Whole Patient

Note: interesting discussion regarding aspirin (anti-inflammatory) and depression

PARP Inhibitor Active in Ovarian Cancer (preliminary studies MK4827) upload date March 22nd

Anatomy for the Gynecologic Oncologist PDF ebook online

Anatomy for the Gynecologic Oncologist PDF ebook online

At 10 U.S. Centers, Cancer Doctors Freeze Babies' Ovaries to Preserve Fertility - TIME Healthland

Expert Review - slides: Renal Cell Carcinoma Biology and the Rationale for VEGF (sorafenib, sunitinib, erlotinib, avastin, interleukins, etc)

Note: if you are unable to access this slide presentation it is because you need to register on the site (free); it may be of interest to those with clear cell ovarian cancer; the largest % of renal cancers are of the clear cell subtype (a known ~75%) ------------------------------------------------------------------------------------------------------- MODULE 1: Renal Cell Carcinoma Biology and Rationale for VEGF Expert review with Lee Lokey, MD, and Brian I. Rini, MD, focusing on renal cell carcinoma
Discussant:	Brian I. Rini, MD—Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, United States
Interviewed by:	Lee Lokey, MD—prIME Oncology, Atlanta, Georgia, United States

published March 21st: Wait Times in Canada--A Comparison by Province

click here for the pdf file


Conclusion
Although there is still much we don’t know, today the picture of wait times across priority areas and provinces is more complete and comparable than in the past. All-Canada estimates indicate that 8 out of 10 patients across the country receive priority procedures (hip, knee, hip fracture repair, cataract and bypass
surgery and radiation treatment) within the time frames that clinical evidence shows is appropriate. That said, the likelihood of receiving treatment within these time frames varies considerably, depending on both the priority area and where one lives in Canada. While there have been some improvements in wait times for priority area procedures over the last three years, these improvements are not being seen consistently across
all procedures or across all provinces. The ability to report these important findings has been enabled by provincial collaboration on measuring and collecting data. Important steps remain in improving consistency of cardiac urgency levels, as well as building more comprehensive diagnostic imaging data before the wait time information can be assessed in a more meaningful way."

Recruitment of newly diagnosed ovarian cancer patients proved challenging in a multicentre biobanking study (UK)

Test Results Management (Canadian Patient Safety/College of Physicians & Surgeons Ontario)

audio interview - critical discussion: CBC.ca | Q | Does "Pink" Serve the Breast Cancer Cause? (and discusses other cancers)

(audio) http://www.cbc.ca/video/news/audioplayer.html?clipid=1608560249

(cbc blog) http://www.cbc.ca/q/blog/2010/10/06/what-do-you-think-about-pink/

updated website links : Lynch syndrome - Gene Tests - DNA tests ordered by healthcare professionals - Genetics Home Reference (international locations/types of tests offerred)

Risk assessment for recurrent venous thrombosis – The Lancet (as it applies to transdermal oestrogens)

Note:  author's response to commentaries on the original research article,  links  included to the discussion

The case for a global rare-diseases registry : The Lancet

The case for a global rare-diseases registry

Rare diseases are a clinically heterogeneous group of about 6500 disorders,1 and in fewer than 200 000 individuals in the USA.2 They are commonly diagnosed during childhood, often inherited, and can have deleterious long-term effects. Although any one condition is rare, their cumulative public health burden is substantial, with 6—8% of people having a rare disease at some point during life.3

Because of the rarity, no single institution, and in many cases no single country, has sufficient numbers of patients to do generalisable clinical and translational research. Geographic spread of patients has been a major impediment to recruitment into clinical trials....cont'd

June 16th - Gynecologic Cancer Conference: Creating Collaborative Care - Agenda | Online Registration by Cvent

worth reading especially the viewpoint: 2 items: editorial (patient consent/genetics) + viewpoint (breaching patient privacy)

Rapid Online Publications

Editorial 

Alerting genetic relatives to a risk of serious inherited disease without a patient’s consent
Graeme K Suthers, Elizabeth A McCusker and Samantha A Wake
   MJA Rapid Online Publication — 24 March 2011
   http://www.mja.com.au/public/issues/194_11_060611/sut11435_fm.html

Viewpoint (blogger's opinion - excellent article)
Doctors breaching patient privacy: Orwell redux
David J Handelsman, Leo A Turner and Ann J Conway
   MJA Rapid Online Publication — 24 March 2011
   http://www.mja.com.au/public/issues/194_11_060611/han10307_fm.html

full free access: Malignant bowel obstruction: Individualized treatment near the end of life

Key points

Combinations of analgesics, antisecretory drugs, and antiemetics can provide acceptable symptom relief.

A venting gastrostomy should be considered if drug therapy fails to reduce nausea and vomiting to an acceptable level.

A nasogastric tube should be used only as a temporizing measure, until symptoms are controlled medically or a venting gastrostomy is placed.

Total parenteral nutrition is beneficial only in patients with intermediate life expectancy who may otherwise die of starvation rather than the cancer itself.

Will Open Government make Canada's health agencies more transparent? -- Canadian Medical Association Journal

"But secrecy and lack of public involvement undermine accountability and the credibility of public institutions and their decisions. They diminish
public trust and feed conspiracy theories."

Prognostic Significance of Splenectomy as Part of Initial Cytoreductive Surgery in Ovarian Cancer

Note:  a similar paper regarding splenectomy - posted on this blog Sept 6, 2010




PURPOSE: 
 We sought to examine how splenectomy as part of up-front cytoreductive surgery in ovarian cancer influences the postoperative course and affects survival.

CONCLUSIONS: 
 The addition of splenectomy to up-front cytoreductive surgery was feasible and safe. However, it appears to carry with it a shortened survival that is unrelated to postoperative morbidity. Our data raise the questions that splenectomy is needed for optimal cytoreduction in more biologically aggressive disease and that splenectomy may be an independent prognostic factor related to depressed immune function.

No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting

of interest: "HE4 was not elevated in endometriosis"
CONCLUSIONS:
The major advantage of HE4 lies in its specificity and improved detection of borderline tumors and early stage ovarian and tubal cancers. HE4 is superior to CA125 with or without RMI and ROMA indices. However, we see no benefit from combining both markers in clinical practice.

Adequacy of risk-reducing gynaecologic surgery in BRCA1 or BRCA2 mutation carriers and other women at high risk of pelvic serous cancer

"...Four serous ovarian cancers and one endometrioid endometrial cancer were detected during surgery or pathological examination.
In conclusion Australasian women attending a specialist gynaecologic oncologist for RRGS (risk reducing gynaecologic surgery) are most likely to have adequate surgery and pathological examination.
Additional education of clinicians and consumers is needed to ensure optimal surgery and pathology in these women."

Improved 5-year disease-free survival for FIGO stage I epithelial ovarian cancer patients without tumor rupture during surgery

Abstract

Objective.

To investigate the impact of perioperative capsule rupture on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with FIGO stage I epithelial ovarian cancer (EOC I).

Methods.

This prospective population-based study enrolled all 279 patients with EOC I diagnosed in Norway between 2002 and 2004. All patients underwent primary surgery. The data were collected from notification reports to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan–Meier plots were used to show differences in DFS and CSS. Cox regression analyses were used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs).

Results.

Significantly more patients in the capsule rupture group (Cr group) had clear cell tumors (28%) than in the FIGO stage IA and IB (AB group: 14%) groups, and the FIGO stage IC (C group: 17%; p < 0.05) group. Despite adjuvant chemotherapy (AC), these patients had a poor 5-year DFS, 94% in the non-AC group and 81% in the AC group (p < 0.01).
After five years of follow-up, there was a lower DFS among patients in the Cr group (79%) and the C group (81%), compared with patients in the AB group (91%; p < 0.05). Independent prognostic factors at the time of diagnosis were grade, histological type, ascites, adhesions, performance status, CA125 and DNA ploidy.
After correcting for the four most important prognostic factors (grade, histological type, ascites, and DNA ploidy), the HR for recurrence was 4.0 (95% CI 1.3–12.7; p < 0.05) for the Cr group and 1.8 (95% CI 0.5–6.1; p = 0.3) for the C group, compared with the AB group.

Conclusions.

Improvement was observed in the 5-year DFS for EOC I patients without tumor rupture during surgery compared with those with tumor rupture. Since AC did not improve the long-term DFS and CSS rates, it is of utmost importance that surgeons avoid tumor rupture during surgery.

Research Highlights

► Impact of perioperative capsule rupture on DFS and CSS in stage I epithelial ovarian cancer.
► The study was prospective and population-based.
► Stage I epithelial ovarian cancer without tumor rupture during surgery has improved at the 5-year DFS.

(U.S.) Patient Advocate Foundation :: 1-800-532-5274

Patient Services

Patient Advocate Foundation offers patient services by telephone to those in need that fall under the scope of our services.
Our professional staff members intervene by making conference calls when needed, assisting with appeals to insurance
companies or the Social Security Administration, negotiating with providers in medical debt situations or securing access to care.
Our staff strive for positive resolutions whenever possible.

Women's Health - Full Text: Preventing familial breast and ovarian cancer: major research advances with little implication

Preventing familial breast and ovarian cancer: major research advances with little implication

Primary prevention of hereditary breast–ovarian cancer syndrome, which accounts for 5–10% of all breast cancer diagnosis, represents a prime paradigm of excellence of personalized medicine [1,2]. However, genetic testing can reveal that BRCA mutation carriers account for less than 25% of the familial risk. There has been little progress in explaining the missing heritability of the remaining 75% of women with family history who test negative for BRCA mutations. Neither recently identified common low-penetrance variants alone, nor their interactions with established environmental risk factors, are able to explain missing heritability. But even among BRCA mutation carriers, the decision by an expert scientific team for the optimal preventive strategy, choosing between prophylactic surgery and intensive surveillance, is very difficult and should be individualized for each woman. Here we discuss the latest advances in breast cancer genetics, their potential to impact prevention strategies and practices, and the future perspectives for a true personalized preventive medicine...........

Missing heritability	ChooseTop of pageRare BRCA mutationsMissing heritability <<Genome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Previous work has suggested the polygenic model to help understand the 75% of breast cancer familial risk [6]. According to this model, the missing heritability could be explained by the accumulation of low to moderate genetic risk variants other than BRCA1/2 genes, namely BRCA3 or BRCA4 high-penetrance genes. Indeed, more than 15 years after the discovery of BRCA1/2 genes, the ‘classical’ linkage studies in high-risk families have identified no other high-penetrance genes. The completion of the HapMap 3 project with a database of common and rare variants [7] and high-throughput screening technology has allowed a new generation of association studies to provide improved understanding of the genetics of familial cancer.

Rare BRCA mutations	ChooseTop of pageRare BRCA mutations <<Missing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Missing heritability	ChooseTop of pageRare BRCA mutationsMissing heritability <<Genome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Genome-wide association studies	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s... <<Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Next generation of GWAS	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWAS <<Whole-genome ...Current practical prevent...ConclusionBiliography

Whole-genome & exome sequencing	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ... <<Current practical prevent...ConclusionBiliography

Current practical preventive approaches	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent... <<ConclusionBiliography

Conclusion	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...Conclusion <<Biliography

Editorial: Dynamic Tension Between Success in a Surgical Career and Personal Wellness: How Can We Succeed in a Stressful Environment and a ‘‘Culture of Bravado"?

full text.pdf Cancer Surgeons’ Distress and Well-being, I: The Tension Between a Culture of Productivity and the Need for Self-Care

(worth reading) Editorial: The Values and Value of Patient-Centered Care -- Epstein and Street 9 (2): 100 -- Annals of Family Medicine

"The originators of client-centered and patient-centered health care were well aware of the moral implications of their work, which was based on deep respect for patients as unique living beings, and the obligation to care for them on their terms. Thus, patients are known as persons in context of their own social worlds, listened to, informed, respected, and involved in their care—and their wishes are honored (but not mindlessly enacted) during their health care journey.^2–6 There have been concerns that patient-centered care, with its focus on individual needs, might be at odds with an evidence-based approach, which tends to focus on populations. Fortunately, that debate has been laid to rest; proponents of evidence-based medicine now accept that a good outcome must be defined in terms of what is meaningful and valuable to the individual patient.⁷ Patient-centered care, as does evidence-based medicine, considers both the art of generalizations and the science of particulars.⁸"

Cochrane Review: abstract - Chemotherapy for malignant germ cell ovarian cancer [Cochrane Database Syst Rev. 2011] - PubMed result

AUTHORS' CONCLUSIONS:
We found only low quality evidence on the use of chemotherapy in malignant germ cell tumours of the ovaries. Therefore we are unable to reach definite conclusions about the relative benefits and harms of chemotherapy use in this disease regardless of disease stage. Due to the benefit of chemotherapy in germ cell cancer of the testis, a trial of chemotherapy versus best supportive care is unlikely to be feasible. Despite this, good quality randomised studies are warranted in this disease to define the role of chemotherapy (type of chemotherapy, duration of treatment, benefit, short and long term toxicities). Given the rarity of this disease, we feel a trans-global approach would be essential in order to perform such trials.

alternate source including professional commentary (gynecologic oncology) link

full free access: (references Dr Folkman 1971) Antiangiogenic Therapies in Epithelial Ovarian Cancer (printer-friendly)

Source: Posted: 03/22/2011; Cancer Control. 2011;18(1):31-43. © 2011 H. Lee Moffitt Cancer Center and Research Institute, Inc.

PLOS Medicine: Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women's Health Initiative: An Analysis of Published Articles

View and Join Ongoing Discussions

Original Article Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women's Health Initiative: An Analysis of Published Articles

0 responses	Promotional Tones - Hormone Therapy after WHI	Posted by sandipniauskas on 23 Mar 2011 at 08:32 GMT
Most recent response on 23 Mar 2011 at 08:32 GMT
2 responses	Pfizer Comment	Posted by cloder on 17 Mar 2011 at 17:54 GMT
Most recent response on 22 Mar 2011 at 20:50 GMT
1 response	Money isn't enough	Posted by lexchin on 16 Mar 2011 at 16:55 GMT
Most recent response on 17 Mar 2011 at 14:27 GMT
0 responses	Follow the money...	Posted by EthicalNag on 16 Mar 2011 at 14:40 GMT
Most recent response on 16 Mar 2011 at 14:40 GMT

Progress Being Made in Genome Sequencing - Medscape interview (in research)

Note: the specific references in this article are colorectal cancer but of interest (re: metastases)

full free access: PROTECT study - Dalteparin versus Unfractionated Heparin in Critically Ill Patients — NEJM (venous thromboembolism-blood clots)

"Venous thromboembolism is an important complication of critical illness.....cont'd

The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group

Methods - Study Design

The trial was conducted in 67 ICUs in academic and community hospitals in Canada, Australia, Brazil, Saudi Arabia, the United States, and the United Kingdom. Recruitment began in May 2006 and, as projected, was completed in 4 years. The trial protocol is available with the full text of this article at NEJM.org.7

android app for Blogger available

blogger android app

in research: Toronto Researchers Create Organic, Non-Toxic Nanoparticle to Find and Treat Tumors

abstract: Healthy eating index and ovarian cancer risk - Cancer Causes and Control

Abstract

The evidence for a role of diet on ovarian cancer prevention remains inconclusive. While many studies have evaluated individual foods and food groups, the evaluation of a comprehensive dietary quality index for predicting cancer risk has received little attention. This study investigates the association between the Healthy Eating Index (HEI), which reflects adherence to the current USDA Dietary Guidelines for Americans and ovarian cancer risk in a population-based case–control study in New Jersey. A total of 205 cases and 390 controls completed the Block 98.2 food frequency questionnaire (FFQ) in addition to reporting on potential risk factors for ovarian cancer. FFQ data were then utilized to calculate the HEI score, and cup, ounce, gram, or caloric equivalents for the 12 different food groups comprising the index. In multivariate models, the OR (overall risk) for the highest tertile of the HEI score compared with the lowest (reflecting a better diet compared with a worse diet) was 0.90 (95% CI: 0.55–1.47).
There was limited evidence for a statistically significant association between any of the 12 individual food components and ovarian cancer risk. Based on this study’s results, neither individual food groups nor dietary quality showed potential for preventing ovarian cancer.

abstract: Genital powder exposure and the risk of epithelial ovarian cancer Cancer Causes and Control, Online First™

Conclusions

The International Agency for Research on Cancer has designated perineal exposure to talc (via the application of genital powders) as a possible carcinogen in women. A modest association of ovarian cancer with this exposure was seen in our study and in some previous ones, but that association generally has not been consistent within or among studies. Therefore, no stronger adjective than “possible” appears warranted at this time.

blog re: NCCN conference - The Coach And The Critic: Stories Of Caregivers Where "Kill Me" Is Not An Option

The Coach And The Critic: Stories Of Caregivers Where "Kill Me" Is Not An Option

What Patients Value When Oncologists Give News of Cancer Recurrence: Commentary on Specific Moments in Audio-Recorded Conversations -- Back et al. 16 (3): 342 -- The Oncologist CME Online

fig 1

Note: full access after registration (free), study design used 'standardized' patients

Definitions of standardized patient:
A simulated patient or standardized patient (SP) (also known as a patient instructor), in health care, is an individual who is trained to act as a real patient in order to simulate a set of symptoms or problems. ...
en.wikipedia.org/wiki/Standardized_patient

Gastroenterology & Endoscopy News - Is Colonoscopy the Optimal Method for Colorectal Cancer Screening? (no specific mention of Lynch Syndrome

Note: no mention of Lynch Syndrome (biology/genetics), full free access with registration (free)

full free access: Research output on primary care in Australia, Canada, Germany, the Netherlands, the United Kingdom, and the United States: bibliometric analysis - bmj.com

What is already known on this topic

• The UK Research Assessment Exercise in 2008 rated 50% of UK primary care research as world class or internationally excellent, but no direct international comparisons exist

What this study adds

• In six countries with strong primary care, the United Kingdom and the Netherlands produce the most cited primary care led primary care research
• Identifying research on primary care that is carried out by primary care researchers is difficult using routine bibliometric methods
• Only 29% of research papers on primary care had at least one primary care researcher as author

Guest post: Absolute risk not as straightforward as you might think - Gary Schwitzer's HealthNewsReview Blog

"...As a Cochrane review pointed out this week (Persuasive health information could be misleading)  (note - this link forwards to a Reuters story) relative risks are very persuasive, but they don't always serve your best interests when making health decisions....:

press release/abstract: Marshall Edwards Announces Publication of Phase II Clinical Trial Results - Phenoxodiol phase 11 ovarian cancer trial results (32 pts)

SAN DIEGO, March 21, 2011 /PRNewswire/ -- Marshall Edwards, Inc.(Nasdaq: MSHL), an oncology company focused on the clinical development of novel therapeutics targeting cancer metabolism, announced today the publication of results from a Phase II clinical trial of intravenous Phenoxodiol in combination with cisplatin in women with platinum-resistant ovarian cancer. The publication is now available on the International Journal of Gynecological Cancer website and scheduled to print in the May issue of the journal......

abstract: Int J Gynecol Cancer. 2011 Mar 15. [Epub ahead of print]

Phase II Evaluation of Phenoxodiol in Combination With Cisplatin or Paclitaxel in Women With Platinum/Taxane-Refractory/Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers.

Clinical Cancer Research Programs Merge To Accelerate Research

The American College of Radiology's Imaging Network (ACRIN) and the Eastern Cooperative Oncology Group (ECOG), National Cancer Institute (NCI) Clinical Trials Cooperative Group members, have announced their intent to merge their clinical cancer research programs.

The groups plan to form an alliance that combines their complementary strengths. The new organization will include three areas of research emphasis: early detection and diagnosis of cancer; biomarker-driven Phase II and Phase III therapeutic studies for multiple cancer types and stages; and genetic, molecular and imaging marker research to predict and monitor treatment response........cont'd

full free access: jan 2011 Cancer and Work - A Canadian Perspective Canadian Association of Psychosocial Oncology

Limited free speech for docs | Columnists | Comment | Calgary Sun

Comments

Sandi Pniauskas
    March 20th 2011, 10:16pm

    "I see no mention of the Institute for Patient Safety and their role in these issues. Aside from selected physicians (the few) who choose to speak up publicly, it's rather a continuing sad situation in Canada. For those who do speak up, healthcare professionals, patients and the public, we seem to ostracize those individuals who have the tenacity to persevere in truth telling and simply trying to do the best possible under often terrible circumstances. More so, where is the peer process in this aside from political fence sitting. There is definitely a need for both federal and provincial ombudsman positions 'with teeth'- to correct these ongoing errors of judgment."

CureToday.com: Spring 2011 Article - "Breaking Out of the Silence"

Genetics of Breast and Ovarian Cancer (PDQ®) - NCI - rare syndrome (LFS, Cowden, PJS)

Other Rare Breast and Ovarian Cancer-Associated Syndromes
Li-Fraumeni syndrome
Cowden syndrome
Peutz-Jeghers syndrome

NIH Video Casting Event Summary - Li-Fraumeni Syndrome (LFS) Workshop - 2010 scientists/physicians/families

video meeting/serves as a starting point for the creation of a LFS research consortium.

Author: NIH Office of Rare Disease and the National Cancer Institute
Runtime: 05:31:06
Download: Download Video
How to download a Videocast
CIT File ID: 16253
CIT Live ID: 9741
Permanent link: http://videocast.nih.gov/launch.asp?16253

Commentary MJA Insight: Henry Woo: Abuse of self-pay patient system widespread (ethics)

Note: sound familiar? 
(to view subscribe(free)

"....Sadly, the abuse of the self-pay system is widespread in the NSW public hospital system. We may be aware that it is happening, but nothing will change unless patients complain, and this is hardly likely.

Surgeons who aren’t happy with this arrangement appear unwilling to come forward in fear of political retribution, professional isolation and stymied career progression.

If we were to abolish self-pay, would we risk throwing the baby out with the bathwater? We have to balance the risks to our professional standing, our inability to regulate this behaviour and the financial risks to those who can least afford it against the risk of removing patient choice.

I would like to see this practice abolished, but if we cannot speak out about this when it involves unethical behaviour, the balance is heavily tilted against ever eradicating the self-pay system in our public hospitals."

Validation of the Histologic Grading for Ovarian Clear Cell Adenocarcinoma: A Retrospective Multi-institutional Study by the Japan Clear Cell Carcinoma Study Group

Abstract
"Pathologic slides from 150 patients with clear cell adenocarcinoma from the collaborating institutions were reviewed independently by 2 pathologists, and each tumor was graded histologically using the Shimizu-Silverberg and International Federation of Gynecology and Obstetrics (FIGO) grading systems...................... These results suggest that the 2 tested grading systems have limited value for the prognostication of patients with clear cell adenocarcinoma, and that a more effective grading system for this tumor may be required."

Physicians as guardians of genetic knowledge : The Lancet

Intll Jnl of Oncology: Ganoderma lucidum (herbal mushrooms) exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin (York University Toronto)

"Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported...................... Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin."

abstract: Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas

CONCLUSIONS:  
OCCCs constitute a heterogeneous disease at the genomic level despite having similar histological features. The pattern of genomic aberrations in subgroups of OCCCs is of clinical significance.

abstract: Mutation and Loss of Expression of ARID1A in Uterine Low-grade Endometrioid Carcinoma

Abstract:

ARID1A is a recently identified tumor suppressor gene that is mutated in approximately 50% of ovarian clear cell and 30% of ovarian endometrioid carcinomas. The mutation is associated with loss of protein expression as assessed by immunohistochemistry.

In this study, we evaluated ARID1A immunoreactivity in a wide variety of carcinomas to determine the prevalence of ARID1A inactivation in carcinomas. Mutational analysis of ARID1A was carried out in selected cases. Immunoreactivity was not detected (corresponding to inactivation or mutation of ARID1A) in 36 (3.6%) of 995 tumors.

Uterine low-grade endometrioid carcinomas showed a relatively high-frequency loss of ARID1A expression, as 15 (26%) of 58 cases were negative. The other tumor that had a relatively high-frequency loss of ARID1A expression was gastric carcinoma (11%). Mutational analysis showed 10 (40%) of 25 uterine endometrioid carcinomas; none of 12 uterine serous carcinomas and none of 56 ovarian serous and mucinous carcinomas harbored somatic ARID1A mutations. All mutations in endometrioid carcinomas were nonsense or insertion/deletion mutations, and tumors with ARID1A mutations showed complete loss or clonal loss of ARID1A expression.

In conclusion, this study is the first large-scale analysis of a wide variety of carcinomas showing that uterine low-grade endometrioid carcinoma is the predominant tumor type harboring ARID1A mutations and frequent loss of ARID1A expression. These findings suggest that the molecular pathogenesis of low-grade uterine endometrioid carcinoma is similar to that of ovarian low-grade endometrioid and clear cell carcinoma, tumors that have previously been shown to have a high-frequency loss of expression and mutation of ARID1A.

Medical News: SGO: Mutation Link to Ovarian Cancer Disputed - in Meeting Coverage, SGO from MedPage (KRAS mutation)

Genomic Health Says Gene Test Alters Breast Cancer Therapy - Businessweek (21 gene test)

Ovarian cancer patient ‘failed by consultant’ (The Bolton News) - case of misconduct

Blogger's note: odd that the story didn't mention how the patient is doing ??

"....The panel heard that at a later consultation, the progress of the condition was again not identified and acted on, with poor notes made.
A specialist was not consulted and clinical standards of care were not met...."

abstract: Informed consent to microsatellite instability and immunohistochemistry screening for Lynch syndrome (ethics/informed consent)

From the 1Department of Bioethics, Cleveland Clinic; 2Genomic Medicine Institute Lerner College of Medicine, Cleveland Clinic; and 3Center for Genomic Research Ethics & Law, Case Western Reserve University, Cleveland, Ohio.

Abstract

OBJECTIVE: Routine microsatellite instability (MSI) and immunohistochemistry (IHC) screening of colorectal cancers can assist in identifying a significant proportion of cancers attributable to Lynch syndrome. This article considers whether it is necessary to obtain patient informed consent for microsatellite instability and immunohistochemistry screening.

RESULTS: Although microsatellite instability screening examines genetic features of a tumor, it lacks several important characteristics that typically mandate formal informed consent to genetic testing. Microsatellite instability screening describes discrete tissue samples and does not provide information about the rest of the patient's body or germline. In contrast, immunohistochemistry screening is a proteomic test that may reveal information about the patient's germline. As such, immunohistochemistry screening can be viewed as similar to other forms of genetic testing, in which explicit patient consent is regarded as an ethical prerequisite.

CONCLUSION: There is no ethical requirement to obtain explicit informed consent for microsatellite instability screening of colorectal tumor samples for Lynch syndrome. There is support for obtaining patient consent to immunohistochemistry testing, given its similarities with other genetic analyses for which informed consent is typically deemed necessary. Regardless of which screening test is used, it is important to prepare patients and their families for the possibility of a positive screening test.

Mar 15th, 2011 - free full access - A National Registry for Healthy Volunteers in Phase 1 Clinical Trials - — JAMA

Nevada news: Nevada Cancer Institute Expands with New Oncologists (gynecologic oncologist)