Research Papers: Pathology:

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

Christian Schafroth, José A. Galván, Irene Centeno, Viktor H. Koelzer, Heather E. Dawson, Lena Sokol, Gregor Rieger, Martin D. Berger, Marion Hädrich, Robert Rosenberg, Ulrich Nitsche, Beat Schnüriger, Rupert Langer, Daniel Inderbitzin, Alessandro Lugli and Inti Zlobec _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:41453-41463. https://doi.org/10.18632/oncotarget.6162

Metrics: PDF 2398 views  |   HTML 3145 views  |   ?  


Christian Schafroth1, José A. Galván1, Irene Centeno1, Viktor H. Koelzer1,2, Heather E. Dawson1,2, Lena Sokol1, Gregor Rieger1,2, Martin D. Berger3, Marion Hädrich4, Robert Rosenberg5, Ulrich Nitsche6, Beat Schnüriger4, Rupert Langer1,2, Daniel Inderbitzin4,7, Alessandro Lugli1,2 and Inti Zlobec1

1 Translational Research Unit, Institute of Pathology, Bern University Hospital, Bern, Switzerland

2 Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland

3 Department of Medical Oncology, Bern University Hospital, Bern, Switzerland

4 Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland

5 Department of Surgery, Kantonsspital Baselland, Liestal, Switzerland

6 Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

7 Department of Surgery, Tiefenau Hospital, Bern, Switzerland

Correspondence to:

Inti Zlobec, email:

Keywords: colorectal cancer, BRAF, VE1, heterogeneity, prognosis, metastasis, Pathology Section

Received: September 22, 2015 Accepted: October 04, 2015 Published: October 19, 2015


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 6162