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BRAF V600E‐specific immunohistochemistry for the exclusion of Lynch syndrome in MSI‐H colorectal cancer
Author(s) -
Capper David,
Voigt Anita,
Bozukova Gergana,
Ahadova Aysel,
Kickingereder Philipp,
von Deimling Andreas,
von Knebel Doeberitz Magnus,
Kloor Matthias
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28183
Subject(s) - lynch syndrome , mlh1 , immunohistochemistry , germline mutation , colorectal cancer , pathology , medicine , cancer , microsatellite instability , cancer research , mutation , biology , dna mismatch repair , genetics , microsatellite , gene , allele
The differentiation between hereditary and sporadic microsatellite‐unstable (MSI‐H) colorectal cancer is a crucial step in Lynch syndrome diagnostics. Within MSI‐H colorectal cancers, the BRAF V600E mutation is strongly associated with sporadic origin. Here, we asked whether BRAF V600E‐specific immunohistochemistry (clone VE1) is helpful in separating sporadic from Lynch syndrome‐associated MSI‐H colorectal cancers. To that end, we performed VE1 immunohistochemistry and BRAF sequencing in a series of 91 MSI‐H colorectal cancer specimens from patients tested for Lynch syndrome. Concordance of VE1 immunohistochemistry and molecular BRAF mutation status was observed in 90 of 91 (98.9%) MSI‐H samples. All 11 tumors classified as BRAF V600E mutation‐positive by Sanger sequencing were immunopositive, and 79 (98.8%) of 80 tumors classified as BRAF wild type showed negative staining. All VE1‐positive tumors were MLH1‐ and PMS2‐negative by immunohistochemistry. None of the tumors from mismatch repair (MMR) gene germline mutation carriers ( n = 28) displayed positive VE1 staining, indicating that BRAF V600E mutation‐specific immunostaining has a low risk of excluding Lynch syndrome patients from germline mutation analysis. In conclusion, implementation of VE1 immunohistochemistry was able to detect BRAF ‐mutated MSI‐H colorectal cancers with a sensitivity of 100% and a specificity of 98.8%. Among MLH1‐negative colorectal cancers, the rate of VE1‐positive lesions was 21%, offering the exclusion of these patients from MMR germline testing. Therefore, we suggest the integration of VE1 immunohistochemistry into the diagnostic panel of Lynch syndrome.