The relationship between microvessel count and the expression of vascular endothelial growth factor, p53, and K-ras in non-small cell lung cancer

Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, an d vascular endothelial growth factor (VEGF) in 61 surgically resected non-s mall cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcino ma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significa ntly higher than that of tumors without LN metastasis (66.1 +/- 23.1 vs. 33 .8 +/- 13.1, p < 0.05). VEGF was positive in 54 patients (88.5%). MC was 58 .1 +/- 25.2 (mean S.D.) in a x 200 field, and it was significantly higher i n VEGF(+) tumors than in VEGF(-) tumors (61.4 +/- 23.7 vs. 32.9 +/- 23.8, p < 0.05). VEGF expression was higher in Kras-positive or mutant p53-positiv e tumors than in negative tumors (p < 0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ accord ing to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusi on, there is a flow of molecular alterations from K-ras and p53, to VEGF ex pression, leading to angiogenesis and ultimately lymph node metastasis. Cor relations between variables in close approximation and the lack of prognost ic significance of individual molecular alterations suggest that tumorigene sis and metastasis are multifactorial processes.