Impact of MET expression on outcome in BRAF V600E/K advanced melanomaстатья из журнала
Аннотация: Aims Preclinical data suggest that signalling through the HGF – MET pathway may confer resistance to BRAF inhibition in BRAF V 600E/K melanoma. Therefore, blockade of HGF – MET signalling might be a valid therapeutic strategy, in combination with BRAF inhibition, in BRAF V 600E/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 V 600E/K advanced melanoma treated with vemurafenib. Methods and results Formalin‐fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM 2 ( n = 59) and BRIM 3 ( n = 150) trials of vemurafenib in advanced BRAF V 600E/K melanoma. Immunohistochemistry for MET ( SP 44 rabbit monoclonal antibody) was performed with a highly validated assay and clinically validated scoring system. Pretreatment MET expression was frequent at the ≥1 + cutoff ( BRIM 3, 31%; BRIM 2, 49%), but relatively infrequent at the ≥2 + cutoff ( BRIM 3, 9%; BRIM 2, 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 V 600E/K advanced melanomas. Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib‐treated melanoma.
Год издания: 2013
Авторы: Adrian M. Jubb, Antoni Ribas, Jeffrey A. Sosman, Grant A. McArthur, Yibing Yan, Sandra Rost, Sherry Zhao, Hartmut Koeppen
Издательство: Wiley
Источник: Histopathology
Ключевые слова: Melanoma and MAPK Pathways, Cutaneous Melanoma Detection and Management, Sarcoma Diagnosis and Treatment
Другие ссылки: Histopathology (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed
Том: 63
Выпуск: 3
Страницы: 351–361