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A review of the clinical relevance of mismatch‐repair deficiency in ovarian cancer
Author(s) -
Pal Tuya,
PermuthWey Jenny,
Sellers Thomas A.
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23601
Subject(s) - mlh1 , dna mismatch repair , microsatellite instability , ovarian cancer , lynch syndrome , medicine , germline mutation , epigenetics , cancer , msh2 , colorectal cancer , germline , pms2 , cancer research , oncology , bioinformatics , mutation , genetics , biology , allele , gene , microsatellite
Abstract Ovarian cancer ranks fifth in both cancer incidence and mortality among women in the United States. Defects in the mismatch‐repair (MMR) pathway that arise through genetic and/or epigenetic mechanisms may be important etiologically in a reasonable proportion of ovarian cancers. Genetic mechanisms of MMR dysfunction include germline and somatic mutations in the MMR proteins. Germline mutations cause hereditary nonpolyposis colorectal cancer (HNPCC), which is the third most common cause of inherited ovarian cancer after BRCA1 and BRCA2 mutations. An epigenetic mechanism known to cause inactivation of the MMR system is promoter hypermethylation of 1 of the MMR genes, mutL homolog 1 ( MLH1 ). Various laboratory methods, in addition to clinical and histopathologic criteria, can be used to identify MMR‐deficient ovarian cancers. Such methods include microsatellite instability analysis, immunohistochemistry, MLH1 promoter hypermethylation testing, and germline mutation analysis. In this review, the authors describe the existing literature regarding the molecular, clinical, and histologic characteristics of MMR‐deficient ovarian cancers along with the possible effect on survival and treatment response. By further defining the profile of MMR‐deficient ovarian cancers and their associated etiologic mechanisms, there may be a greater potential to distinguish between those of hereditary and sporadic etiology. The ability to make such distinctions may be of diagnostic, prognostic, and therapeutic utility. Cancer 2008. © 2008 American Cancer Society.