abstract: Hormone Therapy and Different Ovarian Cancers: A National Cohort Study (postmenopausal women/does not include reference to clear cell ovarian)

 Blogger's Note: the abstract makes no reference to clear cell ovarian, given the number of women followed this omission (in the abstract) is curious


Hormone Therapy and Different Ovarian Cancers: A National Cohort Study

Abstract

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. 

Using Danish national registers, the authors identified 909,946 women who were followed from 1995–2005. The women were 50–79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. 

Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology......... In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. 

Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors and endometrioid tumors but decreased risk of mucinous tumors. Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. 

Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

abstract: Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma.

Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma

Abstract

It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible on the basis of only histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty and 3 fellows) but who were trained in its use by referring to a website designed for the purpose. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (≥4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/reactive was achieved in 76% of the lesions, with no consensus in 24%. Combining diagnoses into 2 categories (STIC versus non-STIC) resulted in an overall consensus of 93% and no consensus in 7%. The κ value for STIC versus non-STIC among all 6 observers was also high at 0.67 and did not significantly differ, whether for faculty (κ=0.66) or fellows (κ=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it to routine clinical practice, the algorithm should be evaluated by general surgical pathologists in a community setting.

abstract: Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type.

Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type [Am J Surg Pathol. 2012]

Abstract

The role of endometriosis in ovarian cancer, disease progression, and survival is a subject of active investigation. A series of 144 ovarian cancers with clear cell or endometrioid histology or associated endometriosis, all classified on the basis of strict histologic criteria, was evaluated to further explore the relationship between endometriosis-associated ovarian cancer and age at presentation, FIGO stage, histology, presence of synchronous primary disease elsewhere in the mullerian tract, and survival.

Patients with endometrioid carcinomas were significantly younger (mean, 52 y) in comparison with patients with either clear cell carcinoma (mean, 55 y) or mixed tumors (mean, 59 y; P=0.002).

Clear cell carcinoma presented as low-stage disease (FIGO I) in 33% of cases compared with endometrioid carcinomas in 97% of cases and mixed carcinomas in 27% of cases. Endometriosis was associated with 53% of clear cell carcinomas, 33% of endometrioid carcinomas, and 45% of mixed tumors (P<0.001). Synchronous primary tumors, observed in 31% of endometrioid tumors, 5% of mixed tumors, and in 2% of clear cell tumors (P<0.001), were unlikely to be associated with endometriosis (P=0.04). Univariate analysis of the aggregate cohort demonstrated that the single best overall predictor of disease-free survival was FIGO stage at presentation (P<0.001), followed by histologic subtype (P=0.003).

Endometriosis did not have a significant relationship with disease-free survival (P=0.7). We conclude that the link between endometriosis and ovarian cancer is much stronger for clear cell carcinoma than for other histologic subtypes (P<0.001). Furthermore, when uniform histologic criteria are applied, true mixed endometrioid and clear cell carcinomas are uncommon; most endometriosis-associated mixed tumors are heterogenous mixtures of endometrioid, mucinous, and serous histology with areas of clear cell cytoplasm. Endometriosis per se does not appear to predict prognosis in clear cell and endometrioid tumors, with the possible exception of tumors with mixed histology. Until more data are collected, pathologists should classify ovarian tumors with mixed histology as a separate and potentially unique biological and prognostic group.

(Apr 2012) Commentary: Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

"Previous large epidemiological studies have attempted to identify benign gynaecological disorders that predispose to the development of epithelial ovarian cancer. The only disorder that has been repeatedly1—4 (although not universally5) associated with this cancer is endometriosis. Results of some of these studies have suggested a specific link with endometrioid and clear-cell ovarian cancers, but until now none had the power to allow definitive subgroup analysis based on a contemporary definition of histological subtype.

 

In a study reported in the Lancet Oncology, Celeste Leigh Pearce and colleagues6 assessed self-reported endometriosis data from 13 pooled case—control studies in the Ovarian Cancer Association Consortium (OCAC). They confirm that a history of endometriosis is significantly associated with an increased risk of clear-cell (odds ratio 3·05, 95% CI 2·43—3·84) and endometrioid (2·04, CI 1·67—2·48) ovarian cancers, and for the first time show an association with low-grade serous ovarian cancer (2·11, 1·39—3·20). No association was noted between endometriosis and high-grade serous, mucinous, serous borderline, or mucinous borderline ovarian cancers.

 

With more than 23 000 participants (7911 with a diagnosis of ovarian cancer), the main strengths of this study are its statistical power and its robust methods. Incidences of reported endometriosis differ substantially between the pooled studies. Although clinicopathological and genetic differences between the populations could reasonably be expected, importantly there was no significant heterogeneity of the association with histological subtype in the different studies.

The main truly novel finding is an association between a history of endometriosis and low-grade serous ovarian cancer. Perhaps surprisingly, serous borderline tumours (from which invasive low-grade serous ovarian cancers are believed to arise7) are not also associated with a history of endometriosis.

open access: Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer — NEJM

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer — NEJM

......"We evaluated the efficacy of olaparib monotherapy as maintenance treatment in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had had a response to their most recent platinum-based chemotherapy......"

In conclusion, the results from this randomized, phase 2 study show that maintenance treatment with olaparib was associated with a significant improvement in progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. However, at the interim analysis, this did not translate into an overall survival benefit. As of this writing, 21% of the patients were still receiving olaparib (and 3% were still receiving placebo), which indicates that the disease is controlled for a prolonged period in some patients.

open access: JTM - Absolute lymphocyte count is associated with survival in ovarian (SEROUS) cancer independent of tumor-infiltrating lymphocytes

  lymphocytesplural of lym·pho·cyte

Noun:

A form of small leukocyte (white blood cell) with a single round nucleus, occurring esp. in the lymphatic system.

 Abstract (provisional)

Background

The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival.

Conclusions

Patients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Medscape: Aurora-B Protein Expression in Stage III Ovarian Carcinoma

"Aims Aurora kinases are central to cell proliferation and considered to be prognostic/predictive markers and therapeutic targets for epithelial cancers. Here, the prognostic/predictive value of Aurora-B protein expression was evaluated in patients with serous, FIGO stage III ovarian carcinomas treated with taxane- or platinum-based first-line chemotherapy (1st-CTx)."

phase 11 - Cancer Research UK launches 'outpatients' (oral)trial of breast and ovarian cancer drug (BRCA/serous cell type - AG-014699 known as Rucaparib or CO-338 - PARP inhibitor)

" Cancer Research UK’s Drug Development Office has re-launched a trial of a promising drug to treat inherited breast and ovarian cancer – but this time taken as a tablet by outpatients."
 
"Women with advanced breast or ovarian cancer with faults in the known high-risk BRCA1 or BRCA2 genes will receive the drug called AG-014699 (Rucaparib) – which belongs to a promising class of drugs called PARP inhibitors. The trial is also open to women with advanced serous ovarian cancer but unknown BRCA status."

"Notes to editors

The drug AG-014699 (also called Rucaparib or CO-338) was recently licenced to Clovis Oncology from Pfizer."

Prognostic significance of L1CAM in ovarian (serous) cancer and its role in constitutive NF-κB activation

Background: Overexpression of L1-cell adhesion molecule (L1CAM) has been observed for various carcinomas and correlates with poor prognosis and late-stage disease. In vitro, L1CAM enhances proliferation, cell migration, adhesion and chemoresistance. We tested L1CAM and interleukin-1 beta (IL-1β) expression in tumor samples and ascitic fluid from ovarian carcinoma patients to examine its role as a prognostic marker.

Conclusions: L1CAM expression contributes to the invasive and metastatic phenotype of serous ovarian carcinoma. L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1β production and NF-κB activation.

Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. 

Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. 

There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). 

Androgen receptor expression is a biological marker for androgen sensitivity in high grade serous epithelial ovarian cancer

Highlights

► Androgen receptor expression correlates with androgen sensitivity in ovarian cancer.
► Androgen receptor expression decreases with chemotherapy.
► Androgen receptor expression is a biomarker for androgen therapy in ovarian cancer.

Cancer Genome Atlas (press release July 2011) TCGA Completes Ovarian Cancer (serous) Analysis - TCGA plus link to video discussion

To view a video of Dr. Spellman discussing TCGA and the ovarian cancer findings, please go to http://www.youtube.com/watch?v=TK_CIGEUHxU

p53 Signature and Serous Tubal In-situ Carcinoma in Cases of Primary Tubal and Peritoneal Carcinomas and Serous Borderline Tumors of the Ovary

press release: UCSF-led team decodes evolution of skin and ovarian cancer cells (squamous cell/serous cell)

"They worked with a type of skin cancer known as cutaneous squamous cell carcinoma, which has among the highest numbers of mutations of any cancer, and also with a common type  (blogger's note: assumption - serous cell type) of ovarian cancer."


"Using the new technique, the researchers were able to identify not just the mutations that differentiate two types of human cancer from normal cells, but the actual order in which some of the most key mutations occurred."
 ...................................................................................................

Temporal Dissection of Tumorigenesis in Primary Cancers

The article, "Temporal Dissection of Tumorigenesis in Primary cancers" is authored by Steffen Durinck, Christine Ho, Nicholas J. Wang, Wilson Liao, Lakshmi R. Jakkula, Eric A. Collisson, Jennifer Pons, Sai-Wing Chan, Ernest T. Lam, Catherine Chu, Kyunghee Park, Sung-woo Hong, Joe S. Hur, Nam Huh, Isaac M. Neuhaus, Siegrid S. Yu, Roy C. Grekin, Theodora M. Mauro, James E. Cleaver, Pui-Yan Kwok, Philip E. LeBoit, Gad Getz, Kristian Cibulskis, Jon C. Aster, Haiyan Huang, Elizabeth Purdom, Jian Li, Lars Bolund, Sarah T. Arron, Joe W. Gray, Paul T. Spellman, and Raymond J. Cho.
It appears in the July 2011 issue of the journal Cancer Discovery. See: http://dx.doi.org/10.1158/2159-8290.CD-11-0028

"Ovarian cancers generally show more complex karyotypic abnormalities than do cSCCs (13)." 

"We sought to validate our observations in an additional
cancer type. Recently, full genomic sequence and copy number
changes were determined for 10 ovarian serous adenocarcinomas
by The Cancer Genome Atlas Project. Ovarian
cancers generally show more complex karyotypic abnormalities
than do cSCCs (13). In the 3 samples with a clear, informative
CN-LOH event at 17p, we again found solid evidence
for complete loss of TP53 as the earliest event (Fig. 1D). These
initial events in ovarian tumorigenesis could not have been
determined through sequencing of precursor lesions and invasive cancers (1, 14), as the asymptomatic nature of early
disease precludes tissue collection." 

The Cancer Genome Atlas completes detailed ovarian cancer analysis - GenOmics

also: A more detailed press release on the study will be available from the National Institutes of Health at http://nih.gov/news/.

full free access: Recent surgical management of ovarian cancer - Journal of Obstetrics and Gynaecology Research

Abstract (also full free access):

Ovarian cancer is the second most common gynecological malignancy in the USA, and the majority of patients with newly diagnosed ovarian cancer present with advanced-stage disease. The standard treatment of these patients involves primary cytoreduction followed by combination chemotherapy. As the evidence has accumulated regarding the benefit of surgical cytoreduction, and as the definition of optimal cytoreduction has evolved, the surgical techniques have expanded in order to achieve this goal. This article discusses the different facets of the surgical management of ovarian cancer, with a special emphasis on the most recent additions to our current knowledge.

Ovarian cancer affects 1 in 70 women, being the second most common gynecological malignancy in the USA. The majority of patients with newly diagnosed ovarian cancer present with advanced-stage disease.1 The standard treatment of these patients involves primary cytoreduction followed by combination chemotherapy.2 As the evidence accumulated regarding the benefit of surgical cytoreduction, and as the definition of optimal cytoreduction evolved, the surgical techniques expanded in order to achieve this goal.

Regardless of the debate on whether it is the biology of the tumor rather than the surgical effort that allows optimal cytoreduction,3,4 and regardless of whether the patient has already received a course of neoadjuvant chemotherapy,5 once the decision to proceed with surgery is taken, its goal should be to achieve maximal cytoreduction.

This article will review the different facets of the surgical management of ovarian cancer, with a special emphasis on the most recent additions to our current knowledge. The data reviewed pertain mainly to high-grade serous carcinoma. Discussing the role of primary versus interval debulking is beyond the scope of this article and will not be reviewed here.

full free access: PLoS ONE: Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis (Mar 15/2011)

Note: research/technical/primary focus on serous cell type

abstract: Tubal ligation and the risk of ovarian cancer: review and meta-analysis — Hum Reprod Update (serous/mucinous/endometrioid)

BACKGROUND The reduction of ovarian cancer (OC) risk in women with a history of tubal ligation (TL) has been reported repeatedly, mostly on small populations. We have aimed to provide a critical overview of the studies available to date and to conduct a meta-analysis.

METHODS There were 40 relevant studies identified. The studies were divided into two groups for strict and extended meta-analysis, respectively. Subgroup analysis was performed for age, time dependency since TL, histological types of OC and BReast CAncer (BRCA) mutation.

RESULTS Meta-analysis of 13 strictly selected studies showed a reduced risk of epithelial OC by 34%. The protective effect of TL was confirmed even in a subgroup of women 10–14 years after the procedure. The risk reduction was confirmed for the endometrioid (RR = 0.40) and serous (RR = 0.73) cancers but not for mucinous.

CONCLUSIONS The review of relevant articles, as well as the meta-analysis of selected studies, yields consistent data on a significant reduction of OC risk in women who had undergone TL. The results of this meta-analysis should provide an impulse for further research on the etiology of ovarian epithelial cancers, focusing particularly on the importance of retrograde transport of endometrial cells.

Mucosal carcinoma of the fallopian tube coexists with ovarian cancer of serous subtype only: a study of Japanese cases

Abstract
Previous studies in Western countries have revealed that mucosal carcinoma of the fallopian tube frequently coexists with pelvic (ovarian, tubal, and peritoneal) serous carcinomas, and early tubal carcinoma is now regarded as a possible origin of these tumors. However, the relationship between early tubal carcinoma and non-serous ovarian cancer, such as clear cell adenocarcinoma, has not been studied in detail. In this study, we sought to examine the coexistence of mucosal carcinoma of the fallopian tube in Japanese ovarian cancer cases. We submitted the fallopian tubes in toto for histological examination in 52 ovarian carcinoma cases and three peritoneal serous carcinoma cases. The ovarian tumors included 12 serous adenocarcinomas, 23 clear cell adenocarcinomas, nine endometrioid adenocarcinomas, three mucinous adenocarcinomas, and four mixed epithelial carcinomas. Mucosal carcinoma of the fallopian tube did not coexist with non-serous adenocarcinoma (n = 40). In contrast, mucosal carcinoma of the fallopian tube was observed in six cases of ovarian serous adenocarcinoma and one case of peritoneal serous adenocarcinoma. In these cases, the p53 immunophenotypes were similar in tubal lesions and invasive ovarian or peritoneal carcinomas. Tumors were negative for p53 in four of seven cases, and one of the p53-negative serous adenocarcinomas showed low-grade morphology. We believe that some ovarian and peritoneal serous adenocarcinomas develop from early tubal carcinomas. However, it should be noted that early tubal carcinomas are not always p53-positive immunohistochemically. Finally, it is unlikely that early tubal lesions are involved in the carcinogenesis of clear cell adenocarcinoma and other non-serous adenocarcinomas.

Serous and mucinous borderline ovarian tumors (LMP): are there real differences between these two entities?

Objective
To evaluate the clinical outcome and pathological features of patients with borderline ovarian tumors (BOT) with special emphasis on serous and mucinous histology.


Conclusions
Serous tumors present more unfavorable anatomopathological characteristics but are associated with better prognosis than mucinous tumors. If mucinous BOT diagnosis is retained physicians should be aware that their aggressive potential is not negligible.