Morphologic and Immunohistochemical Correlation of Ovarian and Tubal Dysplasia in Prophylactic Oophorectomies from BRCA1/2 Mutation Carriers
FM Penault-Llorca, G Chene, MM Dauplat, I Raoelfils, N Lagarde, YJ Bignon, J Dauplat. Centre Jean Perrin, Clermont-Ferrand, France
Background: Histopathological examination of material from prophylactic salpingo-oophorectomies (pBSO) performed in patients at genetic risk has revealed frequent abnormalities interpreted as possible pre-cancerous « ovarian dysplasia » lesions. We sought to study the morphologic features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries.
Design: Morphologic features and immunohistochemical expression patterns of Ki-67, p53 and ALDH1 (an enzyme significantly associated with early-stage ovarian cancer) were evaluated in 35 pBSO from BRCA1/BRCA2 carriers and 30 normal salpingo-oophorectomies (nBSO). Representative slides from formalin-fixed, paraffin-embedded tissue blocks were all read blindly by two gynecological pathologists (FPL & NL). Immunohistochemical staining results were correlated with morphologic findings.
Results: Mean ovarian and tubal dysplasia score were significantly higher in the genetic risk group than in controls (respectively 9.29 vs 3.17, p< 0.0001 for ovaries and 6.54 vs 1.37, p<0.0009 for tubes). Increased ALDH1 expression was observed in pBSO compared with nBSO whereas expression patterns of Ki67 and p53 were low in both groups. Interestingly, ALDH1 expression was low in non dysplastic epithelium, high in dysplasia and constantly low in the carcinoma found incidentally on pBSO.
Conclusions: The increased dysplasia score and ALDH1 expression in ovaries from BRCA1/2 carriers might be consistent with progression towards neoplastic transformation and could justify the use of the term “dysplasia” or intraepithelial ovarian neoplasia. Ovarian and tubal dysplasia may be a pre-malignant, non-invasive histopathological abnormality that could be an important step in early neoplasia, especially in ovaries from BRCA1/2 carriers. The ALDH1 activation in pBSO should be considered as a target for prevention.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 8:15 AM
Platform Session: Section D, Tuesday Morning