Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study.

The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS. ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women. Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years. Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age > 60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age < 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease.

Goodfellow PJ ，Billingsley CC ，Lankes HA ，Ali S ，Cohn DE ，Broaddus RJ ，Ramirez N ，Pritchard CC ，Hampel H ，Chassen AS ，Simmons LV ，Schmidt AP ，Gao F ，Brinton LA ，Backes F ，Landrum LM ，Geller MA ，DiSilvestro PA ，Pearl ML ，Lele SB ，Powell MA ，Zaino RJ ，Mutch D ... -  《-》

Association of tumor morphology with mismatch-repair protein status in older endometrial cancer patients: implications for universal versus selective screening strategies for Lynch syndrome.

Rabban JT ，Calkins SM ，Karnezis AN ，Grenert JP ，Blanco A ，Crawford B ，Chen LM ... -  《-》

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

Buchanan DD ，Tan YY ，Walsh MD ，Clendenning M ，Metcalf AM ，Ferguson K ，Arnold ST ，Thompson BA ，Lose FA ，Parsons MT ，Walters RJ ，Pearson SA ，Cummings M ，Oehler MK ，Blomfield PB ，Quinn MA ，Kirk JA ，Stewart CJ ，Obermair A ，Young JP ，Webb PM ，Spurdle AB ... -  《-》

Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer.

Mills AM ，Liou S ，Ford JM ，Berek JS ，Pai RK ，Longacre TA ... -  《-》

Feasibility of screening for Lynch syndrome among patients with colorectal cancer.

Hampel H ，Frankel WL ，Martin E ，Arnold M ，Khanduja K ，Kuebler P ，Clendenning M ，Sotamaa K ，Prior T ，Westman JA ，Panescu J ，Fix D ，Lockman J ，LaJeunesse J ，Comeras I ，de la Chapelle A ... -  《-》