Impact of MET expression on outcome in BRAFV600E/K advanced melanoma. Issue 3 (26th June 2013)

• Record Type: Journal Article
• Authors: Jubb, Adrian M; Ribas, Antoni; Sosman, Jeffrey A; McArthur, Grant A; Yan, Yibing; Rost, Sandra; Zhao, Sherry; Koeppen, Hartmut
• Is Part Of: Histopathology. Volume 63:Issue 3(2013)
• Page Start: 351
• Page End: 361
• Publication Date: 2013-06-26
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12169
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12169-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12169-sec-0001" sec-type="section"> <title>Aims</title> <p>Preclinical data suggest that signalling through the HGF–MET pathway may confer resistance to BRAF inhibition in BRAF<sup>V</sup><sup>600E/K</sup> melanoma. Therefore, blockade of HGF–MET signalling might be a valid therapeutic strategy, in combination with BRAF inhibition, in BRAF<sup>V</sup><sup>600E/K</sup> 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<sup>V</sup><sup>600E/K</sup> advanced melanoma treated with vemurafenib.</p> </sec> <sec id="his12169-sec-0002" sec-type="section"> <title>Methods and results</title> <p>Formalin‐fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM2 (<italic>n</italic> = 59) and BRIM3 (<italic>n</italic> = 150) trials of vemurafenib in advanced BRAF<sup>V</sup><sup>600E/K</sup> 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.</p> </sec> <sec id="his12169-sec-0003" sec-type="section"> <title>Conclusions</title> <p>MET is expressed in a proportion of BRAF<sup>V</sup><sup>600E/K</sup> advanced melanomas. Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib‐treated melanoma.</p> </sec> </abstract>