Expression of hepatocyte growth factor and c-met protein is significantly associated with the progression of oral squamous cell carcinoma in Taiwan.
BACKGROUND
Hepatocyte growth factor (HGF) is a pleotropic growth factor that regulates cell proliferation, migration, survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its receptor, c-met protein.


METHODS
In this study, we examined the expression of HGF and c-met protein in 93 specimens of oral squamous cell carcinoma (OSCC), 10 specimens of oral epithelial dysplasia (OED), 14 specimens of oral epithelial hyperkeratosis (OEH), and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The HGF and c-met labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of HGF or c-met in OSCCs and clinicopathological parameters, or survival of OSCC patients was analyzed statistically to investigate the possible influence of HGF or c-met on the progression and prognosis of OSCCs in Taiwan.


RESULTS
Positive HGF or c-met staining was mainly cytoplasmic. The mean HGF LI increased significantly from NOM (3.1 +/- 5.1%) through OEH (32.5 +/- 19.8%) and OED (52.0 +/- 19.3%) to OSCC (71.9 +/- 28.6%; P = 0.000). The mean c-met LI also increased significantly from NOM (25.8 +/- 30.8%) and OEH (34.4 +/- 19.3%) through OED (53.0 +/- 20.0%) to OSCC (73.0 +/- 29.4%; P = 0.000). Statistical analysis showed that the c-met LI in either the tumor center or invasion front was significantly associated with T status, N status, and clinical staging of OSCC. However, only the HGF LI in the tumor invasion front was significantly correlated with N status and clinical staging of OSCC.


CONCLUSIONS
Our results suggest that the expression of HGF and c-met protein is an early event in oral carcinogenesis in Taiwan. The HGF LI in the tumor invasion front and the c-met LI in either the tumor center or invasion front can predict the progression of OSCCs in Taiwan.
Chen
Yu-Shan
YS
Graduate Institutes of Oral Biology, National Taiwan University, Taipei, Taiwan.
Wang
Jeng-Tzung
JT
Chang
Yu-Fong
YF
Liu
Bu-Yuan
BY
Wang
Yi-Ping
YP
Sun
Andy
A
Chiang
Chun-Pin
CP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology*; D003593:Cytoplasm / Q000648:ultrastructure; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D007972:Leukoplakia, Oral / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D015996:Survival Rate; D013624:Taiwan
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met