PURPOSE: Although several gene abnormalities have been reported in endometrial carcinoma, the genetic alterations have not fully been elucidated. Recent studies have revealed frequent activating mutations of the gene for BRAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies. However, the prevalence and significance of BRAF mutations in endometrial carcinoma remain unclear. EXPERIMENTAL DESIGN: We examined BRAF mutations in exons 11 and 15 in 97 cases of endometrial carcinoma (endometrioid type, 78; nonendometrioid type, 19), 9 cases of atypical endometrial hyperplasia, and 20 cases of normal endometrium by direct sequencing. In addition, mutations of KRAS and p53 and the immunohistochemical expression of hMLH1 and hMSH2 were also examined. RESULTS: Of the 97 carcinomas and 9 hyperplasias, 20 (21%) and 1 (11%) had BRAF mutations, most of them at previously unreported sites. Twenty samples of normal endometrium and 21 samples of normal endometrium obtained from sites adjacent to neoplastic lesions had no BRAF mutations. There was no apparent difference in the prevalence of BRAF mutation among stages, histologic subtypes, or grades. Mutations of KRAS and p53 were found in 18 (19%) and 22 (23%) cases, and 65 (67%) and 92 (95%) cases showed positive immunostaining for hMLH1 and hMSH2, respectively. BRAF mutation was more frequently found in hMLH1-negative cases (12 of 32, 41%) than in hMLH1-positive cases (7 of 65, 11%; P = 0.008), suggesting that it is associated with an abnormal mismatch repair function. CONCLUSIONS: These findings suggest that mutations of the BRAF gene are partly involved in the malignant transformation of the endometrium.
PURPOSE: Although several gene abnormalities have been reported in endometrial carcinoma, the genetic alterations have not fully been elucidated. Recent studies have revealed frequent activating mutations of the gene for BRAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies. However, the prevalence and significance of BRAF mutations in endometrial carcinoma remain unclear. EXPERIMENTAL DESIGN: We examined BRAF mutations in exons 11 and 15 in 97 cases of endometrial carcinoma (endometrioid type, 78; nonendometrioid type, 19), 9 cases of atypical endometrial hyperplasia, and 20 cases of normal endometrium by direct sequencing. In addition, mutations of KRAS and p53 and the immunohistochemical expression of hMLH1 and hMSH2 were also examined. RESULTS: Of the 97 carcinomas and 9 hyperplasias, 20 (21%) and 1 (11%) had BRAF mutations, most of them at previously unreported sites. Twenty samples of normal endometrium and 21 samples of normal endometrium obtained from sites adjacent to neoplastic lesions had no BRAF mutations. There was no apparent difference in the prevalence of BRAF mutation among stages, histologic subtypes, or grades. Mutations of KRAS and p53 were found in 18 (19%) and 22 (23%) cases, and 65 (67%) and 92 (95%) cases showed positive immunostaining for hMLH1 and hMSH2, respectively. BRAF mutation was more frequently found in hMLH1-negative cases (12 of 32, 41%) than in hMLH1-positive cases (7 of 65, 11%; P = 0.008), suggesting that it is associated with an abnormal mismatch repair function. CONCLUSIONS: These findings suggest that mutations of the BRAF gene are partly involved in the malignant transformation of the endometrium.
Authors: Nur-Afidah Mohamed Suhaimi; Yu Miin Foong; Daniel Yoke San Lee; Wai Min Phyo; Igor Cima; Esther Xing Wei Lee; Wei Lin Goh; Wei-Yen Lim; Kee Seng Chia; Say Li Kong; Min Gong; Bing Lim; Axel M Hillmer; Poh Koon Koh; Jackie Y Ying; Min-Han Tan Journal: Mol Oncol Date: 2015-01-07 Impact factor: 6.603
Authors: Hemant K Bid; Aaron Kibler; Doris A Phelps; Sagymbek Manap; Linlin Xiao; Jiayuh Lin; David Capper; Duane Oswald; Brian Geier; Mariko DeWire; Paul D Smith; Raushan T Kurmasheva; Xiaokui Mo; Soledad Fernandez; Peter J Houghton Journal: Clin Cancer Res Date: 2013-10-16 Impact factor: 12.531
Authors: Irene Lurkin; Robert Stoehr; Carolyn D Hurst; Angela A G van Tilborg; Margaret A Knowles; Arndt Hartmann; Ellen C Zwarthoff Journal: PLoS One Date: 2010-01-21 Impact factor: 3.240