Impact of MET expression on outcome in BRAFV600E/K advanced melanoma

Adrian M. Jubb*, Antoni Ribas, Jeffrey A. Sosman, Grant A. Mcarthur, Yibing Yan, Sandra Rost, Sherry Zhao, Hartmut Koeppen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Aims: Preclinical data suggest that signalling through the HGF-MET pathway may confer resistance to BRAF inhibition in BRAFV600E/K melanoma. Therefore, blockade of HGF-MET signalling might be a valid therapeutic strategy, in combination with BRAF inhibition, in BRAFV600E/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 BRAFV600E/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 BRAFV600E/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 BRAFV600E/K advanced melanomas. Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib-treated melanoma.

Original languageEnglish (US)
Pages (from-to)351-361
Number of pages11
JournalHistopathology
Volume63
Issue number3
DOIs
StatePublished - Sep 1 2013

Keywords

  • BRAF
  • HGF
  • MET
  • Melanoma
  • SP44

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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