Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC.
OBJECTIVE
Non-small cell lung cancer (NSCLC) tissue produces numerous growth factors, which are multifunctional and considered predictive of patient survival. This study sought to evaluate the relationship between concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) in NSCLC tissue and clinicopathological factors, and determine whether these factors correlate with long-term survival.


METHODS
We retrospectively investigated 71 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, for whom the primary curative approach was surgery, and who received no chemotherapy or radiotherapy prior to surgery. bFGF, VEGF, HGF were measured in extracts prepared from these 71 frozen tissue samples by ELISA. Five- and 10-year survival was obtained to determine the most important predictors of long-term survival.


RESULTS
Among clinicopathological parameters, the mean concentration of bFGF was significantly higher in tissue extracts from cases involving metastatic nodal involvement (87.5+/-69.3 ng/100 mg protein) than in those without nodal involvement (57.6+/-42.5 ng; P<0.05). Levels of VEGF in adenocarcinoma (26.8+/-34.0 ng) were higher than for squamous cell carcinoma (12.2+/-13.8 ng; P<0.05). HGF levels also demonstrated histological differences (14.7+/-7.7 vs. 10.6+/-9.7 ng, P<0.05). bFGF protein levels were basically the same, but showed no statistically significant differences with respect to histological type (72.5+/-55.2 vs. 63.6+/-51.5 ng). Patients with high levels of bFGF or VEGF showed significantly worse survival rates than patients with low levels (P=0.0059; P=0.0134). In particular, high concentrations of both bFGF and VEGF correlated with markedly poor prognosis (P<0.0001). Multivariate analysis indicated that lymph node involvement and levels of bFGF and VEGF were independent prognostic factors in cases of NSCLC (adenocarcinoma or squamous cell carcinoma) involving patients who had undergone curative resection.


CONCLUSIONS
Adenocarcinoma associated with lung cancer is regarded to have biological characteristics that distinguish it from squamous cell carcinoma. Node invasion may be associated with bFGF. bFGF and VEGF augment each other and are associated with leading to poor prognosis. The results of this study suggests that effective therapy to block angiogenesis may need to address at least both of these factors in cases of NSCLC.
Iwasaki
Akinori
A
Second Department of Surgery, Fukuoka University, School of Medicine, 45-1-7 Chome Jonan-Ku, Nanakuma, Fukuoka 814-0180, Japan. akinori@fukuoka-u.ac.jp
Kuwahara
Motohisa
M
Yoshinaga
Yasuteru
Y
Shirakusa
Takayuki
T
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality; D008207:Lymphatic Metastasis; D008297:Male; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2