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Takashi Nakashima, Cheng-long Huang, Dage Liu, Kotaro Kameyama, Daiki Masuya, Masaki Ueno, Reiji Haba, Hiroyasu Yokomise
Med Sci Monit 2004; 10(6): BR157-165
Background:Understanding and controlling angiogenesis and lymphangiogenesis could lead to effective strategies for cancer treatment. The aim of our study was to clarify the clinical value of vascular endothelial growth factor-A (VEGF-A) and VEGF-C in non-small cell lung cancer (NSCLC).Material/Methods: One hundred and fifty-three patients with NSCLCs were studied to investigate intratumoral expression of VEGF-A and VEGF-C by immunohistochemistry. Simultaneously, we evaluated tumor angiogenesis using CD34 immunostaining.Results: Seventy-eight carcinomas (51.0%) were VEGF-A-positive, and 64 carcinomas (41.8%) were VEGF-C-positive. There was no correlationship between VEGF-A expression and VEGF-C expression in NSCLCs. The frequency of hypervascular tumors was significantly higher in VEGF-A-positive NSCLCs than in VEGF-A-negative NSCLCs (p=0.0442), while there was no correlation between intratumoral VEGF-C expression status and tumor vascularity. Concerning survival of NSCLC patients, intratumoral expression of VEGF-A was one of the significant prognostic factors in NSCLC patients (relative risk=2.012, p=0.0101), especially in patients with adenocarcinomas (relative risk=3.816, p=0.0025). On the other hand, intratumoral expression VEGF-C was one of the significant prognostic factors in patients with squamous cell carcinomas (relative risk=3.946, p=0.0143).Conclusions: The present study demonstrated that intratumoral VEGF-A expression is one of the significant prognostic factors in patients with adenocarcinomas, and that intratumoral VEGF-C expression is one of the significant prognostic factors in patients with squamous cell carcinomas. These different functions of the VEGF family in relation to tumor histology might reflect the clinical behaviors of NSCLCs.