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Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases.
Am J Surg Pathol. 2016 May; 40(5):656-63.AJ

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

26813747

Citation

Bennett, Jennifer A., et al. "Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases." The American Journal of Surgical Pathology, vol. 40, no. 5, 2016, pp. 656-63.
Bennett JA, Morales-Oyarvide V, Campbell S, et al. Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. Am J Surg Pathol. 2016;40(5):656-63.
Bennett, J. A., Morales-Oyarvide, V., Campbell, S., Longacre, T. A., & Oliva, E. (2016). Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. The American Journal of Surgical Pathology, 40(5), 656-63. https://doi.org/10.1097/PAS.0000000000000602
Bennett JA, et al. Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. Am J Surg Pathol. 2016;40(5):656-63. PubMed PMID: 26813747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. AU - Bennett,Jennifer A, AU - Morales-Oyarvide,Vicente, AU - Campbell,Sharon, AU - Longacre,Teri A, AU - Oliva,Esther, PY - 2016/1/28/entrez PY - 2016/1/28/pubmed PY - 2016/8/30/medline SP - 656 EP - 63 JF - The American journal of surgical pathology JO - Am J Surg Pathol VL - 40 IS - 5 N2 - 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. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/26813747/Mismatch_Repair_Protein_Expression_in_Clear_Cell_Carcinoma_of_the_Ovary:_Incidence_and_Morphologic_Associations_in_109_Cases_ L2 - https://doi.org/10.1097/PAS.0000000000000602 DB - PRIME DP - Unbound Medicine ER -