The Incidence of Microsatellite Instability in Synchronous Endometrial and Ovarian Endometrioid Adenocarcinomas: A Dilemma Revisited.
Shirley M Shiller, Sarah E Kerr, Joseph H Blommel, Ande M Rumilla, Kevin C Halling, Stephen N Thibodeau, Fabiola Medeiros. Mayo Clinic, Rochester, MN
Background: Because Lynch Syndrome more frequently affects patients with synchronous (rather than single) colorectal cancer, intuitively, the same principle would seem to apply to women with synchronous gynecologic primaries. Current literature is inconsistent regarding the prevalence of microsatellite instability (MSI) in this population, with reported rates between 0 and 47%. Moreover, it is unknown whether it is appropriate to test one or both tumors in synchronous cases. This study aims to answer these questions in an unselected series of women with presumed synchronous endometrial and ovarian endometrioid adenocarcinomas.
Design: Histopathologic review of 42 candidate synchronous endometrial and ovarian endometrioid adenocarcinomas over a 12-year-period produced 27 cases in which there was consensus among three pathologists regarding endometrioid histology and synchronicity based on published criteria. Bilateral ovarian tumors were tolerated in the absence of a parenchymal growth pattern (9 cases), in which cases, both were tested. All formalin-fixed, paraffin embedded tumors were tested by MSI PCR (Promega MSI Analysis System, v1.2, Promega Corporation, Madison, WI.) and immunohistochemistry (IHC) for DNA mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6.
Results: All synchronous cases (tumor pairs/trios) had identical results for any one woman. Twenty-one cases were microsatellite stable with normal IHC. Six of 27 (22%) cases were microsatellite unstable (microsatellite instability-high, MSI-H). Five of these cases demonstrated loss of MLH1 and PMS2 expression; the remaining MSI-H case demonstrated normal MMR expression.
Conclusions: The incidence of MSI-H synchronous endometrioid adenocarcinomas closely matches the incidence of MSI in patients with single endometrial cancer (approximately 20%). Because IHC loss of MLH1 and PMS2 is often associated with somatic MLH1 promoter hypermethylation in the tumor, only a fraction of these patients are predicted to have a germline mutation (i.e., Lynch syndrome). The results suggest that screening patients with synchronous endometrioid tumors is no better or worse than screening a general population with only uterine cancer. In addition, the findings indicate that a single specimen may be acceptable for molecular screening in synchronous cases.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 135, Monday Morning