Flt-4-positive endothelial cell density and its clinical significance in non-small cell lung cancer.
OBJECTIVE
Experimental studies have revealed that fms-like tyrosine kinase (Flt)-4 plays important roles in lymphangiogenesis in malignant tumors, but the clinical significance remains unclear. We assessed Flt-4 expression in tumor cells and in endothelial cells in correlation with clinical outcomes in non-small cell lung cancer (NSCLC).


METHODS
A total of 206 consecutive patients with resected pathological stage I-IIIA NSCLC were reviewed. Expression of Flt-4 was examined immunohistochemically, and Flt-4-positive microvessels were quantitatively evaluated (Flt-4-positive endothelial cell density).


RESULTS
There was no significant correlation between Flt-4-positive endothelial cell density and any characteristic of patients including nodal metastases. A significant correlation between Flt-4-positive endothelial cell density and Flt-4 status in tumor cells was documented (P < 0.001), but there was no significant difference in the mean Flt-4-positive endothelial cell density according to vascular endothelial growth factor-C or -D status in tumor cells. The 5-year survival rate for higher Flt-4-positive endothelial cell density tumor (56.4%) was significantly lower than that of lower Flt-4-positive endothelial cell density tumor (69.0%, P = 0.046); the prognostic significance was enhanced in pIIIA-N2 patients (5-year survival rates, 18.8% for higher Flt-4-positive endothelial cell density tumor and 50.0% for lower Flt-4-positive endothelial cell density tumor, respectively; P = 0.012). A multivariate analysis confirmed that higher Flt-4-positive endothelial cell density was a significant and independent prognostic factor (P = 0.019). CD34-positive vessel density or Flt-4 status in tumor cells was not a significant prognostic factor.


CONCLUSIONS
Flt-4-positive endothelial cell density, not Flt-4 status in tumor cells, was a significant prognostic factor in NSCLC.
Chen
Fengshi
F
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Takenaka
Kazumasa
K
Ogawa
Eiji
E
Yanagihara
Kazuhiro
K
Otake
Yosuke
Y
Wada
Hiromi
H
Tanaka
Fumihiro
F
D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D014408:Biomarkers, Tumor; D042442:Vascular Endothelial Growth Factors; D040321:Vascular Endothelial Growth Factor Receptor-3