BRAF mutation in sporadic colorectal cancer and Lynch syndrome

被引：69

作者：

Thiel, Alexandra ^{[1
,2
,3
,4
]}

Heinonen, Mira ^{[1
,2
,3
,4
]}

Kantonen, Jonas ^{[1
,2
,3
,4
]}

Gylling, Annette ^{[5
]}

Lahtinen, Laura ^{[6
]}

Korhonen, Mari ^{[7
]}

Kytola, Soili ^{[7
]}

Mecklin, Jukka-Pekka ^{[8
,9
]}

Orpana, Arto ^{[7
]}

Peltomaki, Paivi ^{[5
]}

Ristimaki, Ari ^{[1
,2
,3
,4
]}

机构：

[1] Univ Helsinki, Cent Hosp, HUSLAB, Div Pathol & Genet,HUS, FIN-00029 Helsinki, Finland

[2] Univ Helsinki, Cent Hosp, Haartman Inst, HUS, FIN-00029 Helsinki, Finland

[3] Univ Helsinki, HUS, FIN-00029 Helsinki, Finland

[4] Univ Helsinki, Res Programs Unit, FIN-00029 Helsinki, Finland

[5] Univ Helsinki, Dept Med Genet, FIN-00029 Helsinki, Finland

[6] Cent Hosp Cent Finland, Dept Pathol, Jyvaskyla, Finland

[7] Univ Helsinki, Cent Hosp, HUSLAB, Genet Lab, FIN-00029 Helsinki, Finland

[8] Univ Eastern Finland, Jyvaskyla Cent Hosp, Dept Surg, Jyvaskyla, Finland

[9] Univ Eastern Finland, Inst Clin Med, Jyvaskyla, Finland

来源：

VIRCHOWS ARCHIV | 2013年 / 463卷 / 05期

基金：

芬兰科学院;

关键词：

BRAF; Colorectal cancer; Lynch syndrome; MLH1; Microsatellite instability; Methylation; MICROSATELLITE INSTABILITY; V600E MUTATION; TISSUE SAMPLES; STAGE-II; IMMUNOHISTOCHEMISTRY; METHYLATION; EXPRESSION; HNPCC; IDENTIFICATION; CARCINOMAS;

D O I：

10.1007/s00428-013-1470-9

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

The aim of the study was to detect mutations of BRAF oncogene in colorectal cancer and to use this information to identify Lynch syndrome patients. Consecutive cases of primary colorectal cancer (n = 137) were analyzed for MLH1 protein expression using immunohistochemistry (IHC). BRAF V600E mutation was detected by IHC using a specific monoclonal antibody (VE1) and by qPCR. All MLH1 protein-negative cases were subjected to microsatellite instability analysis and MLH1 promoter methylation assay. MLH1 protein expression deficiency and high microsatellite instability (MSI-H) were detected in 18 of the 137 (13.1 %) consecutive colorectal cancer specimens. Detection of the BRAF V600E mutation by IHC was 100 % sensitive and specific as compared to qPCR, and this mutation was frequently present in the MSI-H group (77.8 %; 14/18) and less frequently in the microsatellite-stable group (7.6 %; 9/118). All BRAF V600E mutated cases of the MSI-H group presented with a MLH1 promoter methylation (14/14) as detected by methylation-specific multiplex ligation-dependent probe amplification. When BRAF was wild type in the MSI-H group, only one MLH1 promoter methylation was detected (1/4), and of the remaining three cases without MLH1 methylation, two were identified to harbor an MLH1 mutation consistent with Lynch syndrome. Finally, 11 previously confirmed Lynch syndrome cases were analyzed for BRAF V600E mutation, and all of them were wild type. In conclusion, detection of BRAF V600E in colorectal cancer specimens by IHC is sensitive and specific and may help to identify Lynch syndrome patients.

引用

页码：613 / 621

页数：9

共 36 条

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