c-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas.

Koji Tsuta, Yoshiki Kozu, Takahiro Mimae, Akihiko Yoshida, Takashi Kohno, Ikuo Sekine, Tomohide Tamura, Hisao Asamura, Koh Furuta, Hitoshi Tsuda

Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. ktsuta@ncc.go.jp

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2012 Feb

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The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. The aim of this study was to examine the correlations between c-MET/phospho-MET expression as well as MET gene copy number alterations and overall survival (OS) in non-small cell lung carcinomas (NSCLCs). We analyzed 906 NSCLCs including 704 adenocarcinomas (ADCs), 150 squamous cell carcinomas (SCCs), 43 sarcomatoid carcinomas, and 9 large cell carcinomas. The mutational status of epidermal growth factor receptor and K-ras and anaplastic lymphoma kinase rearrangements were retrospectively examined. We performed immunohistochemistry to detect c-MET/phospho-MET expression and MET gene copy number using bright-field in situ hybridization (BISH). c-MET/phospho-MET expression and MET BISH positivity were observed in 22.2%, 5.6%, and 10.9% of NSCLCs, respectively; they were more prevalent in ADCs (27.3%, 6.9%, and 11.5%, respectively) and sarcomatoid carcinomas (20.9%, 9.3%, and 36.6%, respectively) than in SCCs and large cell carcinomas. Among ADCs, poorly differentiated cases exhibited c-MET expression and MET BISH positivity more commonly than well-differentiated ones. An analysis of all patients revealed that c-MET/phospho-MET expression and MET BISH positivity were not correlated with OS. However, when SCC cases were excluded, both univariate (p=0.019) and multivariate (p=0.020) analyses revealed a significant correlation between MET BISH positivity and OS. c-MET/phospho-MET expression and MET BISH positivity differed according to histological type. Among ADCs, c-MET expression and MET BISH positivity were more common in poorly differentiated cases. MET BISH positivity was an independent prognostic factor in nonsquamous NSCLCs.

Citation

Koji Tsuta, Yoshiki Kozu, Takahiro Mimae, Akihiko Yoshida, Takashi Kohno, Ikuo Sekine, Tomohide Tamura, Hisao Asamura, Koh Furuta, Hitoshi Tsuda. c-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2012 Feb;7(2):331-9