Genetic Instability in Serous Tubal Intraepithelial Carcinoma and Tubo-Ovarian Dysplasia from Prophylactic Oophorectomies for Genetic Risk
Frederique Penault-Llorca, Andrei Tchirkov, Ines Raoelfils, Anne Cayre, Eleonore Pierre, Philippe Vago, Gautier Chene. Centre Jean Perrin, Clermont-Ferrand, France; CHU, Clermont-Ferrand, France
Background: Through BRCA and P53 alterations, genetic instability plays an important contribution in ovarian carcinogenesis. We sought to study telomere shortening and surrogate markers of genetic instability in early and pre-invasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC) and tubo-ovarian dysplasia (TOD).
Design: 51 tubo-ovarian dysplasia from bilateral prophylactic oophorectomies (pBSO) with BRCA1 (36) or BRCA2 (15) mutation (defined by morphological score and immunohistochemical expression of p53, ALDH1 and gH2AX), 12 STICs, 53 ovarian high grade serous carcinoma and 36 control bilateral oophorectomies (nBSO) were laser-capture microdissected on formalin-fixed paraffin-embedded sections and analyzed by comparative genomic hybridization (CGH array) and for telomere length (T/S using quantitative real-time polymerase chain reaction based on the Cawthon technique (Nucleic Acid Res 2002 30:1-6)).
Results: We found few subtle genomic alterations in dysplastic epithelium in opposition to the important genomic imbalances in STICs and ovarian cancers. STICs had the shortest telomeres followed by TOD in pBSO (respectively, T/S= 7.23 and T/S= 18.78). Ovarian carcinoma (T/S= 30.68) had shorter telomeres than nBSO (T/S= 52.75) but longer than STICs and dysplasia.
All these differences were statistically significant. When comparing telomere lenght in dysplasia from BRCA1 and BRCA2 pBSO, the shortest telomeres were observed in BRCA1 carriers.
Conclusions: These findings suggest that genetic instability occurs at early stages of ovarian and tubal carcinogenesis. Targeting genetic instability might be an option for prevention in high risk patients, but requires further studies.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 138, Tuesday Afternoon