Uncertainty in the Utility of Mismatch Repair Protein Expression measured by Immunohistochemistry in a Multicenter Population-based Study of Epithelial Ovarian Cancer

immunohistochemistry (IHC) for MMR protein expression. Although the utility of IHC has been demonstrated in colorectal cancer, its utility in ovarian cancer remains incompletely defined. We sought to evaluate the loss of protein expression of the MMR proteins (MLH1, MSH2 and MSH6) in three population-based samples of epithelial ovarian cancers. Methods: IHC staining was performed on full section slides or tissue microarray (TMA) slides for MLH1, MSH2, and MSH6 protein expression in paraffin-embedded tumor samples. Samples were considered to have loss of expression (LoE) if one or more proteins had an expression score of < 3 (on a scale of 9). Collection of demographic, clinical and family history information was attempted in all women. Results: Of 487 participants in whom IHC was completed, 147 were performed through full section slides and 340 were performed through TMA slides. In the overall sample, LoE of one or more of the MMR proteins was observed in 12.7%. Notably, the proportion of tumors with LoE was significantly higher in TMAs (17.9%) compared to full section slides (0.7%) (p <0.001). Finally, tumors with loss of MMR protein expression were more likely to be from individuals with tumors of non-serous histology (p=0.004). Conclusions: A substantial proportion of epithelial ovarian cancers have a loss of MMR protein expression. Protein expression results vary significantly by the tissue sampling methodology utilized, raising concerns about the clinical utility of this test for ovarian tumors.