VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer

Schafroth, Christian; Galván Hernández, José Alberto; Centeno Ramos, Irene; Kölzer, Viktor; Dawson, Heather; Sokol, Lena; Rieger, Gregor; Berger, Martin D; Hädrich, Marion; Rosenberg, Robert; Nitsche, Ulrich; Schnüriger, Beat; Langer, Rupert; Inderbitzin, Daniel; Inderbitzin, Daniel; Lugli, Alessandro; Zlobec, Inti (2015). VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer. OncoTarget, 6(39), pp. 41453-41463. Impact Journals LLC 10.18632/oncotarget.6162

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AIM VE1 is a monoclonal antibody detecting mutant BRAFV600E protein by immunohistochemistry. Here we aim to determine the inter-observer agreement and concordance of VE1 with mutational status, investigate heterogeneity in colorectal cancers and metastases and determine the prognostic effect of VE1 in colorectal cancer patients. METHODS Concordance of VE1 with mutational status and inter-observer agreement were tested on a pilot cohort of colorectal cancers (n = 34), melanomas (n = 23) and thyroid cancers (n = 8). Two prognostic cohorts were evaluated (n = 259, Cohort 1 and n = 226, Cohort 2) by multiple-punch tissue microarrays. VE1 staining on preoperative biopsies (n = 118 patients) was compared to expression in resections. Primary tumors and metastases from 13 patients were tested for VE1 heterogeneity using a tissue microarray generated from all available blocks (n = 100 blocks). RESULTS Inter-observer agreement was 100% (kappa = 1.0). Concordance between VE1 and V600E mutation was 98.5%. Cohort 1: VE1 positivity (seen in 13.5%) was associated with older age (p = 0.0175) and MLH1 deficiency (p < 0.0001). Cohort 2: VE1 positivity (seen in 12.8%) was associated with female gender (p = 0.0016), right-sided tumor location (p < 0.0001), higher tumor grade (p < 0.0001) and mismatch repair (MMR)-deficiency (p < 0.0001). In survival analysis, MMR status and postoperative therapy were identified as possible confounding factors. Adjusting for these features, VE1 was an unfavorable prognostic factor. Preoperative biopsy staining matched resections in all cases except one. No heterogeneity was found across any primary/metastatic tumor blocks. CONCLUSION VE1 is highly concordant for V600E and homogeneously expressed suggesting staining can be analysed on resection specimens, preoperative biopsies, metastatic lesions and tissue microarrays.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology > Autopsy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Galván Hernández, José Alberto; Centeno Ramos, Irene; Kölzer, Viktor; Dawson, Heather; Sokol, Lena; Rieger, Gregor; Hädrich, Marion; Schnüriger, Beat; Langer, Rupert; Inderbitzin, Daniel; Inderbitzin, Daniel; Lugli, Alessandro and Zlobec, Inti

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

18 Jan 2016 14:08

Last Modified:

26 Mar 2016 00:14

Publisher DOI:

10.18632/oncotarget.6162

PubMed ID:

26496026

Uncontrolled Keywords:

BRAF; Pathology Section; VE1; colorectal cancer; heterogeneity; metastasis; prognosis

BORIS DOI:

10.7892/boris.74596

URI:

https://boris.unibe.ch/id/eprint/74596

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