c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis

Cancer Sci. 2007 Jul;98(7):1006-13. doi: 10.1111/j.1349-7006.2007.00493.x. Epub 2007 Apr 24.


c-Met is often overexpressed in non-small cell lung cancer, but it remains unsolved whether its overexpression leads to its activation. We used an antibody specific to phospho-c-Met (Tyr1235) to investigate c-Met activation immunohistochemically in 130 surgically resected lung adenocarcinomas. The expression of c-Met and hepatocyte growth factor (HGF) was also investigated. Phospho-c-Met was positive in 21.5% (28/130) of cases. c-Met was positive in 74.6% of cases (97/130) and was expressed at high levels in 36.1% of cases (47/130). HGF was expressed at high levels in 31.5% of cases (41/130). Phospho-c-Met was correlated with high levels of HGF (P =0.0010) and high levels c-Met expression (P = 0.0303), but it was also found to be positive in 12 cases with little to no HGF expression. Phospho-c-Met expression was significantly associated with tumor differentiation (P = 0.0023) and papillary histology (P = 0.0011), but not with pathological stage, lymph node metastasis or survival. High levels of c-Met and HGF were also associated with papillary histology (P = 0.0056 and P = 0.0396, respectively), but not with tumor differentiation. Phospho-c-Met was correlated with phospho-Akt (P = 0.0381), but not with phospho-Erk or phospho-Stat3. Phospho-Akt expression was marginally correlated with the expression of phospho-epidermal growth factor receptor (EGFR) (P = 0.0533) and, importantly, it was strongly correlated with the expression of either phospho-c-Met or phospho-EGFR (P = 0.0013). The data suggest that in lung adenocarcinoma tissue, c-Met activation may take place either ligand-dependently or ligand-independently via c-Met overexpression. c-Met activation may play special roles in the papillary subtype and in well differentiated lung adenocarcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Cell Differentiation
  • Enzyme Activation
  • Female
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-met / metabolism*
  • Survival Analysis


  • Phosphoproteins
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met