Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer.
BACKGROUND
Angiogenesis plays an important role in tumorigenesis and has attracted interest as a potential target in cancer treatment.


METHODS
We examined the prognostic value of the expression of vascular endothelial growth factor (VEGF) and of the VEGF receptors (VEGFRs) fms-like tyrosine kinase receptor-1 (flt-1) and kinase insert domain-containing receptor (KDR) in non-small-cell lung cancer (NSCLC). Sixty patients with surgical stage I NSCLC who had not undergone induction therapy or adjuvant therapy were selected from among 170 patients with NSCLC who had undergone surgery from January to December 1995. Specimens obtained at surgical resection were subjected to immunohistological staining, and the relationship between postoperative outcome and the expression of VEGF and its receptors was investigated. All patients included in the analysis had been followed up for 5 years or longer or until death.


RESULTS
Patients with tumors expressing VEGF or KDR tended to have poorer outcomes, and VEGF expression and KDR expression were positively correlated. In contrast, flt-1 expression was not correlated with VEGF expression or outcome. Outcomes were poor in patients with tumors positive for both VEGF and VEGFRs. Multivariate analysis identified expression of both flt-1 and KDR and VEGF and KDR as possible independent prognostic factors.


CONCLUSIONS
Our results suggest that expression of VEGF and VEGFR are associated with a poor prognosis via autocrine and paracrine growth stimulation of cancer cells. Moreover, tumors expressing both flt-1 and KDR may have greater malignant potential and are associated with a poor prognosis.
Seto
Takashi
T
Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan. tseto@nk-cc.go.jp
Higashiyama
Masahiko
M
Funai
Hiroko
H
Imamura
Fumio
F
Uematsu
Kazutsugu
K
Seki
Nobuhiko
N
Eguchi
Kenji
K
Yamanaka
Takeharu
T
Ichinose
Yukito
Y
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2