title: Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases.
abstract: Several morphologic features have been reported to be predictive of abnormal expression of mismatch repair (MMR) proteins in endometrial and colon carcinomas. Although it is known that abnormal MMR expression is increased in frequency in ovarian endometrioid and clear cell carcinomas, no such histologic correlation has been identified. We reviewed 109 unselected ovarian clear cell carcinomas for specific tumor characteristics (architecture, nuclear atypia, signet ring cells, stromal hyalinization, background precursor) and inflammatory response (peritumoral lymphocytes found along the leading edge of the tumor, intratumoral stromal inflammation found within the tumor, percentage of plasma cells in the intratumoral stromal inflammation, tumor-infiltrating lymphocytes) and performed immunohistochemistry for all 4 MMR proteins. Abnormal MMR expression was identified in 6% of tumors and included MSH2/MSH6 (3), MLH1/PMS2 (1), MSH6 (1), and PMS2 (1). These patients had a mean age of 40 (range, 31 to 48) years, which contrasted with a mean of 53.2 (range, 28 to 82) years for the overall cohort. One had a concurrent diagnosis of endometrial carcinoma, whereas another had a family history of endometrial carcinoma. None had a personal/family history of colonic carcinoma. Tumors with diffuse intratumoral stromal inflammation and peritumoral lymphocytes were more frequently associated with MMR loss on univariate analysis (P<0.001 and 0.047, respectively) with diffuse intratumoral stromal inflammation remaining a significant independent predictor on multivariate analysis. None of the other morphologic features evaluated reached statistical significance. Although previous series have been unable to identify a relationship between histology and MMR expression, this study identified a correlation with diffuse intratumoral stromal inflammation and peritumoral lymphocytes, 2 features that potentially could be selected for MMR analysis if corroborated by other studies.
authors.affiliation: Departments of *Pathology ‡Surgery, Massachusetts General Hospital, Boston †Department of Pathology, Lahey Hospital and Medical Center, Burlington, MA §Department of Pathology, Stanford University, Stanford, CA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bennett
authors.forename: Vicente
authors.initials: V
authors.lastname: Morales-Oyarvide
authors.forename: Sharon
authors.initials: S
authors.lastname: Campbell
authors.forename: Teri A
authors.initials: TA
authors.lastname: Longacre
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000251:Adenosine Triphosphatases / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001900:Boston / Q000453:epidemiology; D002140:California / Q000453:epidemiology; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes