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Endometriosis-Associated Ovarian Cancer: Poor Clinical Reputation?
Abstract & Commentary
By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman reports no financial relationship to this field of study.
Synopsis: Endometriosis-associated ovarian cancer has improv ed survival compared to conventional epithe ial ovarian cancer due in large part to the frequency of low-grade lesions in these uncommon cancers.
Source: Kumar S, et al. Prognostic analysis of ovarian cancer associated with endometriosis. Am J Obstet Gynecol 2011;204:63.e1-7.
Endometriosis is a common disorder in reproductive-age women and has been associated with an increased risk for development of invasive ovarian cancer. The histology of endometriosis-associated ovarian cancers (EAOCs) appears to be distributed differently compared to conventional ovarian cancer (OC), with clear cell and endometrioid tumors being diagnosed more frequently. The prognostic impact of these unique tumors was evaluated in this retrospective study. Over an 11-year period, 42 patients with EAOC and 184 patients with OC were identified. The diagnosis of EAOC was carefully made according to established histological criteria (Sampson's criteria), which included: (1) clear documentation of endometriosis in proximity to the tumor, (2) no other primary site for the tumor, and (3) the presence of tissue resembling endometrial stroma surrounding epithelial glands, in addition to the demonstration of histologically proven transition from endometriosis to cancer. Data were collected regarding age, stage, histology, grade, surgical features, postoperative management, and survival (progression-free and overall survival). EAOC patients were more likely to be younger, have low-grade and early-stage tumors, be of clear cell or endometrioid histology, and have longer median overall survival compared to patients with OC. By multivariate analysis, only grade was independently predictive of overall survival when controlling for age, stage, race, and surgical cytoreduction. EAOC is a unique condition with improved survival characteristics largely explained by earlier stage at presentation and lower grade tumors.
The clinical course of endometriosis-associated ovarian cancer has been variably and confusingly characterized in the literature. Some reports have suggested improved survival compared to typical ovarian cancer, while others have failed to document any difference.1 Some of the discrepancy has arisen from inconsistent definitions of what constitutes EAOC. The authors of the current retrospective report took great strides to precisely define the condition based on previously established pathological criteria. Of the several distinctions made comparing EAOC to common epithelial ovarian cancer, the difference in histology, stage, and grade are among the most interesting and important from both prognostic and therapeutic point of view. It is from this careful data collection that prognostic factors associated with improved overall survival was observed in patients with EAOC. This was largely due to the higher frequency of low-grade lesions, which was most pronounced among advanced stage patients.
Recent ovarian cancer research has revealed that a specific gene deletion is associated with particular types of ovarian cancer, the very cancers that are associated with EAOC.2 Recently, a mutation in the ARID1A gene was observed in nearly 50% of ovarian clear cell carcinomas and one-third of endometrioid carcinomas; this mutation was absent in all 76 high-grade serous cancers evaluated.3 This gene encodes for a protein (BAF250a), which is a key component of the chromatin-remodeling complex and is also seen in preneoplastic endometriotic lesions. This raises the hypothesis that dysregulation of this pathway is an early event driving the development of EAOC. Such characterizations add further fuel to the discussion that ovarian cancer, like several other solid tumors, should be classified on functional (or biological) terms, rather than by morphological (or appearance). The impact these new discoveries bring to the clinical discussion is exciting since this information can be used to develop new targeted therapeutics; further, these new innovative therapies could be introduced instead of, or in addition to, conventional chemotherapy or more importantly, before invasive malignant disease is discovered.