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

Research output: Contribution to journalArticle

97 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

Fingerprint

Gene Dosage
Non-Small Cell Lung Carcinoma
In Situ Hybridization
Proteins
Adenocarcinoma
Large Cell Carcinoma
Squamous Cell Carcinoma
Carcinoma
Survival
Hepatocyte Growth Factor
Epidermal Growth Factor Receptor
Immunohistochemistry

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

Cite this

C-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. / Tsuta, Koji; Kozu, Yoshiki; Mimae, Takahiro; Yoshida, Akihiko; Kohno, Takashi; Sekine, Ikuo; Tamura, Tomohide; Asamura, Hisao; Furuta, Koh; Tsuda, Hitoshi.

In: Journal of Thoracic Oncology, Vol. 7, No. 2, 02.2012, p. 331-339.

Research output: Contribution to journalArticle

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, vol. 7, no. 2, pp. 331-339. https://doi.org/10.1097/JTO.0b013e318241655f
Tsuta, Koji ; Kozu, Yoshiki ; Mimae, Takahiro ; Yoshida, Akihiko ; Kohno, Takashi ; Sekine, Ikuo ; Tamura, Tomohide ; Asamura, Hisao ; Furuta, Koh ; Tsuda, Hitoshi. / C-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. In: Journal of Thoracic Oncology. 2012 ; Vol. 7, No. 2. pp. 331-339.
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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.",
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AU - Yoshida, Akihiko

AU - Kohno, Takashi

AU - Sekine, Ikuo

AU - Tamura, Tomohide

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AU - Furuta, Koh

AU - Tsuda, Hitoshi

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