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Impact of MET expression on outcome in BRAF(V600E/K) advanced melanoma.

Jubb AM, Ribas A, Sosman JA, McArthur GA, Yan Y, Rost S, Zhao S, Koeppen H
Histopathology. 2013 63 (3): 351-61

PMID: 23802768 · DOI:10.1111/his.12169

AIMS - Preclinical data suggest that signalling through the HGF-MET pathway may confer resistance to BRAF inhibition in BRAF(V600E/K) melanoma. Therefore, blockade of HGF-MET signalling might be a valid therapeutic strategy, in combination with BRAF inhibition, in BRAF(V600E/K) melanoma. The aim of this study was to investigate the clinical relevance of these observations by evaluating the survival impact of MET expression in patients with BRAF(V600E/K) advanced melanoma treated with vemurafenib.

METHODS AND RESULTS - Formalin-fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM2 (n = 59) and BRIM3 (n = 150) trials of vemurafenib in advanced BRAF(V600E/K) melanoma. Immunohistochemistry for MET (SP44 rabbit monoclonal antibody) was performed with a highly validated assay and clinically validated scoring system. Pretreatment MET expression was frequent at the ≥1 + cutoff (BRIM3, 31%; BRIM2, 49%), but relatively infrequent at the ≥2 + cutoff (BRIM3, 9%; BRIM2, 19%). Retrospective subset analyses showed that, irrespective of the cutoff used or the treatment arm, MET expression did not show prognostic significance, in terms of objective response rate, progression-free survival, or overall survival.

CONCLUSIONS - MET is expressed in a proportion of BRAF(V600E/K) advanced melanomas. Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib-treated melanoma.

© 2013 John Wiley & Sons Ltd.

MeSH Terms (25)

Adolescent Adult Aged Aged, 80 and over Animals Disease-Free Survival Female Humans Immunohistochemistry Indoles Kaplan-Meier Estimate Male Melanoma Middle Aged Mutant Proteins Prognosis Proto-Oncogene Proteins B-raf Proto-Oncogene Proteins c-met Rabbits Retrospective Studies Signal Transduction Skin Neoplasms Sulfonamides Vemurafenib Young Adult

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