paywalled - Unravelling the two entities of endometrioid ovarian cancer: A single center clinical experience

Unravelling the two entities of endometrioid ovarian cancer: A single center clinical experience

Purchase

---

Abstract

Objective

Due to the increasing prevalence of the benign condition, ovarian carcinoma arising from endometriosis is emerging as a relevant clinical entity with an unclear biological signature. We have investigated clinical and histologic features of endometriosis-associated endometrioid ovarian cancer using an institutional retrospective database.

Methods

Patients diagnosed with endometrioid ovarian cancer at our institution were divided into two groups according to the fulfillment or not of Sampson's and Scott's criteria for the detection of endometriosis-associated ovarian cancer. Clinical and histological data were reported and compared. Survival analysis was obtained using the log-rank test in an unadjusted Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model to establish independent factors associated with endometriosis-associated endometrioid ovarian cancer and to identify predictors of survival.

Results

Patients with endometriosis-associated endometrioid ovarian cancer were significantly younger, had a lower disease stage (77% vs 38%; p = 0.003), a less prevalent high grade tumor (38% vs 82%; p = 0.002) and a higher prevalence of squamous and mucinous metaplasia. 

The rate of endometrial cancer diagnosis was significantly higher in women with endometriosis-associated endometrioid ovarian cancer (33%) than in other patients (11%) (p = 0.04) with a 92% concordance between ovarian and endometrial histologic tumor grade. A significant difference in survival rate could not be demonstrated between patients with or without endometriosis.

Conclusions

The analysis of a retrospective endometrioid ovarian cancer database may allow to suggest a molecular, morphological and clinical parallelism between endometrial and endometrioid ovarian cancer.

---

Highlights

► Endometriosis-associated endometrioid ovarian tumors possess a different biologic signature when compared to cancers not associated with the disease.
► Clinical course and molecular alterations of type I and type II endometrial tumors are similar to those detected respectively in endometriosis-associated and non-associated endometrioid ovarian tumor.

(click on pdf for full paper) Gynecologic Oncology Case Reports: A Case of Endometrial Cancer in the Context of a BRCA2 Mutation and Double Heterozygosity for Lynch Syndrome

Gynecologic Oncology Case Reports | Articles in Press | ScienceDirect.com

A Case of Endometrial Cancer in the Context of a BRCA2 Mutation and Double Heterozygosity for Lynch Syndrome

In Press, Accepted Manuscript, Available online 15 March 2012
Ping Gong, Sarah Charles, Norman Rosenblum, Zoe Wang, Agnieszka K. Witkiewicz

 Show preview  |   PDF (458 K)   |   Related articles  |  Related reference work articles    

Highlights

► Endometrial cancer with BRCA2 mutation and double heterozygosity for Lynch syndrome 

► Loss of MLH1 and PMS2 by immunohistochemical stain 

► MSH1 and MSH6 gene mutations by genomic sequencing

open access (pdf): Endometrial cancer genomics and genetics (of interest to Lynch Syndrome women/dual malignancies eg. ovarian/uterine cancers)

Endometrial cancer genomics and genetics


Abstract: (click on pdf for full file)

Most sporadic endometrial cancers (ECs) can be histologically classified as endometrioid, serous, or clear cell.

Each histotype has a distinct natural history, clinical behavior, and genetic etiology. Endometrioid ECs have an overall favorable prognosis.

They are typified by high frequency genomic alterations affecting PIK3CA, PIK3R1, PTEN, KRAS, FGFR2, ARID1A (BAF250a), and CTNNB1 (β-catenin), as well as epigenetic silencing of MLH1 resulting in microsatellite instability.

Serous and clear cell ECs are clinically aggressive tumors that are rare at presentation but account for a disproportionate fraction of all endometrial cancer deaths. Serous ECs tend to be aneuploid and are typified by frequent genomic alterations affecting TP53 (p53), PPP2R1A, HER-2/ERBB2, PIK3CA, and PTEN; additionally, they display dysregulation of E-cadherin, p16, cyclin E, and BAF250a.  

The genetic etiology of clear cell ECs resembles that of serous ECs, but it remains relatively poorly defined. A detailed discussion of the characteristic patterns of genomic alterations that distinguish the three major histotypes of endometrial cancer is reviewed herein.

abstract: Does the FIGO 2009 Endometrial Cancer Staging System More Accurately Correlate With Clinical Outcome in Different Histologies?: Revised Staging, Endometrial Cancer, Histology

Blogger's Note: of interest to our ovarian cancer communities eg. dual/concurrent malignancies; Lynch Syndrome
               ~~~~~~~~~~~~~~~~

Does the FIGO 2009 Endometrial Cancer Staging System More Accurately Correlate With Clinical Outcome in Different Histologies?: Revised Staging, Endometrial Cancer, Histology:

Objective:In 2009, the International Federation of Gynecology and Obstetrics (FIGO) staging system was revised for endometrial cancers. Different histologies were examined in a large population database. The FIGO 1988 and 2009 staging systems were compared for stage at presentation, differences in patient populations, and disease-specific survival (DSS).

Methods/Materials:
A total of 10,839 cases from 1998 to 2006 were analyzed from the Surveillance, Epidemiology, and End Results (SEER) Program. Examined histologies included 1377 cases of clear cell carcinoma (CC), 2304 cases of uterine papillary serous carcinoma (PS), 755 cases of carcinosarcoma (CS), and 6403 cases of grade 3 endometrial adenocarcinoma (G3A). The median follow-up was 26 months. For each stage and histology, DSS for patient characteristics was examined.

Results:
Of the 10,839 women with CC, PS, CS, and G3A had a median age of 67 years. White, black, and other ethnicities composed 87.5%, 12%, and 7% of this group, respectively.
A higher percentage of non-G3A histology (CS, PS, and CC) was found in 58% of black women versus 39% of white women. The best to worst 5-year DSS was G3A (76.2%), CC (68.8%), PS (59%), and CS (53.4%). Patients with FIGO IIIC2 disease had inferior survival outcomes in CC (P = 0.0079) and G3A (P = 0.047) compared with FIGO IIIC1 disease, whereas DSS was not significantly different for CS and PS between stages IIIC1 and IIIC2.

Conclusions:
These findings describe differences in the DSS of various aggressive histologies of EC, with poorer DSS in PS, CC, or CS histologies. Analysis demonstrated the usefulness of the new FIGO staging for DSS prediction between stages IIIC1 and IIIC2 for CC and G3A, and 2 divisions for stage I rather than three.


IGCS and ESGO

abstract: Use of Mismatch Repair Immunohistochemistry and Microsatellite Instability Testing: Exploring Canadian Practices

METHODS:

Two web-based questionnaires were administered, a general and a specialist laboratory questionnaire, to establish the availability of such tests, requisite clinical/pathology integration, current mode of test initiation, reporting and recommendation practices, and education and attitudes among pathologists. Technical aspects were reviewed on the basis of specialist laboratory practice.

RESULTS:

Of 76 respondents, 21.5% were unaware or were uncertain whether they had access to MMR immunohistochemistry. Although 78.9% of respondents had access to such testing, an integrated approach to the identification of patients with LS is lacking, being limited to just 9 centers. The majority (70%) of testing is clinician initiated, with variable implementation of reflex testing and divergent practices in recommendation to test. Standardized reporting is lacking in many centers. Education on MMR in endometrial cancer is poor compared with that in colorectal cancer (P<0.0001).

(Blogger's Note: and so it would be safe to assume, based on this abstract, that the full spectrum of Lynch Syndrome related cancers requires obviously increased attention. As a further note, this and similar abstracts should take the opportunity to detail, in the background section, the full cancer spectrum - a one-line sentence is all that is required.)

INTERPRETATION:

This multicenter questionnaire highlights heterogenous practices in dMMR testing and LS identification, both in clinical terms and with regard to technical aspects of testing. An integrated multidisciplinary approach is lacking, and there is a need to educate physicians and resolve ethical issues. A Canadian consensus statement and national guidelines on dMMR testing are urgently needed, requiring input from pathologists, clinicians, and genetic counselors.

abstract: Correlation between body mass index and prevalence of hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in korean patients (endometrial cancer)

CONCLUSION:
However, BMI proportions in the patients with HNPCC related to endometrial cancer was significantly different from those in sporadic endometrial cancer. Specifically, among nonobese patients, the proportion of normal weight was significantly high in Korean women with HNPCC.

Best way to screen for Lynch syndrome in women with endometrial cancer identified - - ModernMedicine (U of B.C./BCCA)

"Because endometrial (uterine) cancers associated with Lynch syndrome most likely present at an earlier age than colorectal cancer -- which is also commonly associated with the syndrome -- screening in these women could provide benefit and help extend overall life expectancy.

Testing all women with endometrial cancer would carry substantial costs, so researchers led by Dr. Janice Kwon, of the University of British Columbia and the British Columbia Cancer Agency in Vancouver, performed a cost-benefit analysis to determine the ideal screening criteria."...

Caveats and Concerns With New Study on Hormone Therapy and Breast Cancer

Note: references studies - WHI (Women's Health Initiative) and California Teachers Study

Clinicians vary in their approaches to HT, said Dr. Ursin. "Certain gynecologists are very careful with finding the right dose for each woman, and some even prescribe [estrogen] alone for women who have a uterus, but then monitor the uterus carefully. Please keep in mind that the risk of breast cancer associated with EPT is relatively moderate. The risk of endometrial cancer with [estrogen] alone is much higher — a more than 4-fold increase in risk in this same population of California teachers," she said.

Medical News: SGO: Hint of Chemoprevention Potential for Lynch Syndrome (endometrial cancers) - in Meeting Coverage, SGO

SAN FRANCISCO -- Oral contraceptives and medroxyprogesterone acetate (MPA, DepoProvera) may have potential as chemopreventive agents for endometrial cancer in women with Lynch syndrome, biomarker data from a small randomized trial suggest.
"Despite the favorable results, Lu noted that the trial required six years to complete, as investigators in the multicenter study had to screen 708 patients to identify 51 who met entry criteria and agreed to participate, including undergoing two endometrial biopsies three months apart."

read the full article & then my comments as below:

Without the benefit of the full paper, I found this article, in part to be quite confusing. In particular "screened women with diagnosed Lynch syndrome". While the first paragraph of the article reflects the focus on endometrial cancer in women with Lynch Syndrome, the paragraph as below, could also be interpreted to include ovarian cancer as well. So, were ovarian cancer patients with Lynch Syndrome included in this study? Chemoprevention in the form of oral contraceptives in the general ovarian cancer populations is well understood, whether or not this applies to ovarian cancer women with Lynch Syndrome may be yet to be determined.
Clarification, please?
Sandi Pniauskas

"To examine the chemopreventive effects of oral contraceptives and DepoProvera in women with Lynch syndrome, investigators conducted a randomized phase II clinical trial. They screened women with diagnosed Lynch syndrome and evaluated them with transvaginal ultrasound and endometrial biopsy."