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BRAF mutation in sporadic colorectal cancer and Lynch syndrome
Ist Teil von
Virchows Archiv : an international journal of pathology, 2013-11, Vol.463 (5), p.613-621
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2013
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.