BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer

• Verfasst von: Capper, David [VerfasserIn]
• Verfasst von: Voigt, Anita Yvonne [VerfasserIn]
• Verfasst von: Bozukova, Gergana [VerfasserIn]
• Verfasst von: Ahadova, Aysel [VerfasserIn]
• Verfasst von: Vollmuth, Philipp [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Verfasst von: Kloor, Matthias [VerfasserIn]
• Titel: BRAF V600E-specific immunohistochemistry for the exclusion of Lynch syndrome in MSI-H colorectal cancer
• Verf.angabe: David Capper, Anita Voigt, Gergana Bozukova, Aysel Ahadova, Philipp Kickingereder, Andreas von Deimling, Magnus von Knebel Doeberitz and Matthias Kloor
• E-Jahr: 2013
• Jahr: 30 March 2013
• Umfang: 7 S.
• Fussnoten: Gesehen am 25.02.2021
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2013
• Band/Heft Quelle: 133(2013), 7, Seite 1624-1630
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.28183
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: BRAF V600E
• Sach-SW: colorectal cancer
• Sach-SW: hereditary nonpolyposis colorectal cancer
• Sach-SW: Lynch syndrome
• Sach-SW: microsatellite instability
• K10plus-PPN: 1749474115

Abstract

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.