Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer.

Abstract

The expression of mRNAs for vascular endothelial growth factor (VEGF) was examined in 42 cases of primary lung cancer tissues (18 adenocarcinomas, 18 squamous cell carcinomas, 2 large cell carcinomas, 3 small cell carcinomas, and 1 adenoid cystic carcinoma) and 4 human lung cancer cell lines. As seen by reverse transcription-PCR analysis, VEGF mRNAs were expressed predominantly as transcripts for the secretory forms of VEGF (VEGF121 and VEGF165), both in resected lung cancer tissues and in human lung cancer cell lines. The positive ratios of VEGF mRNA according to pathological type were 66.7% (12 of 18) in adenocarcinoma, 72.2% (13 of 18) in squamous cell carcinoma, 100% (2 of 2) in large cell carcinoma, and 67% (2 of 3) in small cell carcinoma. The relative antigen levels of VEGF detected by immunohistochemical examination almost coincided with the relative VEGF mRNA expression levels. Also, we examined the expression of basic fibroblast growth factor mRNA in the same tumor specimens. However, no significant correlation was found between the VEGF and basic fibroblast growth factor mRNA expression levels. We assessed the relationship between the VEGF121 mRNA expression level and the survival period in patients (n = 17) who underwent a curative operation at stage I of the disease. The median survival of the VEGF high-expression group was 8 months, and that of the VEGF low-expression group was 151 months. The 3- and 5-year survival rates of the high-expression group (n = 6) were 50.0% and 16.7%, respectively. On the other hand, those of the low expression group (n = 11) were 90.9% and 77.9%, respectively. The difference in survival between the two groups was significant (P < 0.05). Among eight cases of long-term survival beyond 5 years, seven cases had low or no VEGF121 mRNA expression. In contrast, among 18 cases with VEGF121 mRNA overexpression, 17 cases died due to recurrence. As a marker of tumor angiogenesis, the VEGF121 mRNA expression level may be a significant prognostic indicator of lung cancers in early stages.