Ovarian Tumors in Lynch Syndrome: Genotype-Phenotype Correlation.
Paul Ryan, Aaron Pollett, Anna Marie Mulligan, Melyssa Aronson, Patricia Shaw, Janice Kwon, Steven Gallinger, William D Foulkes, Blake Gilks, Blaise A Clarke. Mount Sinai Hospital, Toronto, Canada; Bon Secours Hospital, Cork, Ireland; St. Michael's Hospital, Toronto, Canada; Vancouver General Hospital, BC, Canada; University Health Network, Toronto, Canada; McGill University, Montreal, Canada
Background: The ovary is the second commonest site of gynecologic malignancy in Lynch syndrome. To date there have been limited data on genotype-phenotype correlation in these tumors, or on the sensitivity of clinical screening schemas – Amsterdam II (AmII), revised Bethesda (rBethesda), and Society of Gynecologic Oncologists (SGO) genetic risk assessment schemas – questions examined in this study.
Design: Ovarian cancer cases were identified retrospectively from the records of the cancer registries in Toronto, Vancouver and Montreal. Detailed patient family pedigrees, tumor microsatellite instability (MSI), MMR gene product immunohistochemistry (MMR-IHC), and pathology were correlated with genotype.
Results: Of 15 cancer registry cases identified (mean age 42.8 years, range 31-53 yrs, 1 > 50 years old) – 12 MSH2, 3 MLH1mutations – ovarian cancer was the sentinel tumor in 12 patients (all aged 50 or under), with 3 others having antecedent colorectal cancer. Tumors were unilateral, ovary-confined in 7 cases with 4 of these having synchronous endometrial carcinoma. Histologic types included endometrioid (3), clear cell (2), serous (2), mucinous (1), squamous cell (1) and mixed (6) tumors. Analysis of family pedigrees showed clinical schemas selected the following number of cases: AmII – 7/15 (47%); rBethesda – 5/15 (33%); SGO 20-25% risk – 9/15 (60%); SGO 5-10% risk – 14/15 (93%).
Conclusions: The newer SGO criteria have better sensitivity for detection of Lynch syndrome-related ovarian carcinomas than colorectal cancer-centred schemas such as AmII and rBethesda. The wide spectrum of histologic types and age profile of patients with sentinel tumors suggests any proposed screening algorithm for Lynch syndrome in ovarian carcinoma should consider starting with all patients 50 and under.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 113, Tuesday Afternoon