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

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109 Citations (Scopus)

Abstract

Introduction: 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). Methods: 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). Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)331-339
Number of pages9
JournalJournal of Thoracic Oncology
Volume7
Issue number2
DOIs
Publication statusPublished - 2012 Feb
Externally publishedYes

Keywords

  • Bright-field in situ hybridization
  • C-MET
  • MET gene copy number
  • Non-small cell lung carcinoma
  • Phospho-MET

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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  • Cite this

    Tsuta, K., Kozu, Y., Mimae, T., Yoshida, A., Kohno, T., Sekine, I., Tamura, T., Asamura, H., Furuta, K., & Tsuda, H. (2012). C-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. Journal of Thoracic Oncology, 7(2), 331-339. https://doi.org/10.1097/JTO.0b013e318241655f