c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis.
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.
Nakamura
Yu
Y
Department of Human Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Niki
Toshiro
T
Goto
Akiteru
A
Morikawa
Teppei
T
Miyazawa
Keiji
K
Nakajima
Jun
J
Fukayama
Masashi
M
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000368:Aged; D002454:Cell Differentiation; D004789:Enzyme Activation; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D016019:Survival Analysis
D010750:Phosphoproteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met