Early Genomic Instability in Tubo-Ovarian Preneoplastic Lesions
Gauthier Chene, Andrei Tchirkov, Eleonore Pierre, Jacques Dauplat, Nina Radosevic-Robin, Anne Cayre, Frederique Penault-Llorca. Centre Jean Perrin and EA 4677 ERTICA University of Auvergne, Clermont-Ferrand, France; Estaing Hospital and EA 4677 ERTICA University of Auvergne, Clermont-Ferrand, France; Centre Jean Perrin and EA 4677 ERTICA University of Auvergne, Clermont Ferrand, France
Background: Genetic instability plays an important contribution in ovarian carcinogenesis. We investigated the molecular mechanisms underlying the telomere shortening in early and pre-invasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC), precancerous serous tubal intraepithelial lesions (STIL) and ovarian dysplasia (OD).
Design: 51 STIL and OD from prophylactic salpingo-oophorectomies with BRCA1 mutation, 12 STICs, 43 high-grade serous ovarian carcinoma and 36 non cancerous controls were laser-capture microdissected from formalin-fixed paraffin-embedded sections, analyzed by comparative genomic hybridization (array CGH) and for telomere length (using quantitaive real-time polymerase chain reaction based on the Cawthon method). STIL, OD and STIC were defined by morphological scores and immunohistochemical expressions of p53, Ki67 and gammaH2AX.
Results: We found few subtle genomic alterations in dysplastic epithelium from STIL and OD in opposition to the more important genomic imbalances in STIC (most common regions with gain in chromosomes 19q, 16p, 12q, 10q and 11q and with loss in chromosomes 3q, 2q and 11q). The total number of genetic alterations was the highest in ovarian cancers. STIC had the shortest telomeres followed by STIL and OD (p< 0.007). Ovarian carcinoma had shorter telomeres than non cancerous controls (p<0.01) but statistically longer than STIC, STIL and OD. We found also a statistical correlation between gH2AX expression and telomere shortening (p=0.0016).
Conclusions: These findings suggest that genetic instability occurs in early stages of ovarian tumorogenesis. STICs and non invasive lesions are probably an important step in early serous ovarian neoplasia.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 174, Wednesday Morning