Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by inherited mutations in DNA mismatch-repair genes, most commonly MLH1 or MSH2. The role MSH6 plays in inherited cancer susceptibility is less well defined. The aim of this study was to investigate the penetrance and expressivity of MSH6 mutations in kindreds ascertained through endometrial cancer probands unselected for family history. Detailed pedigrees were constructed for six MSH6 mutation carriers. All reported cancers and precancers were confirmed, and tissues were obtained when available. Tumors were analyzed for microsatellite instability (MSI) and for expression of MSH2, MLH1, and MSH6. MSH6 mutation status was determined for 59 family members. Of these 59 individuals, 19 (32%) had confirmed cancers and precancers. There was an excess of mutation carriers among the 19 affected family members (11 [58%] of 19) compared with those among the 40 unaffecteds (8 [20%] of 40, P=.0065, odds ratio = 5.5, 95% CI = 1.66-18.19). In four of the seven tumors analyzed from mutation carriers other than the probands, MSI and/or MMR protein expression was consistent with the involvement of MSH6. Overall estimated penetrance of the MHS6 mutations was 57.7%. Of the tumors in mutation carriers, 78% were part of the extended HNPCC spectrum. This study demonstrates that MSH6 germline mutations are, indeed, associated with increased cancer risk and that the penetrance of mutations may be higher than appreciated elsewhere. A combination of MSI and immunohistochemistry analyses may be helpful in screening for MSH6 mutation carriers.
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PMID:Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history. 1509 77

Endometrial cancer is the most common gynecologic cancer in developed countries and is rising in incidence globally. Although the 5-year survival rates are >80%, factors beyond conventional pathologic features that predict clinical outcomes are still being elucidated. The aims of this study were to define the prevalence and associations of deficient mismatch repair (dMMR) protein expression (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry in a multiethnic Southeast Asian cohort with endometrioid endometrial cancer. A total of 77 patients with adequate formalin-fixed paraffin-embedded specimens were identified. The sections were stained in 2 centers for 4 MMR proteins and examined by 2 independent specialist histopathologists. The mean age for the cohort was 58.6 yr, with 19.4% (15/77) of patients' cancers showing loss of 2 MMR proteins. All 13 cancers with absent MLH1 showed PMS2 loss (13/15), whereas absent MSH2 correlated with MHS6 loss (2/15). There were no significant differences for dMMR cases in age, body mass index, histopathologic characteristics, and clinical outcomes. In dMMR cases, an overrepresentation of patients of Indian ethnic origin was observed compared with Chinese and Malays. These findings suggest that dMMR protein expression in a Southeast Asian endometrial cancer cohort does not correlate with disease outcomes.
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PMID:The immunohistochemistry signature of mismatch repair (MMR) proteins in a multiethnic Asian cohort with endometrial carcinoma. 2527 93