Vascular Endothelial Growth Factor 189 Mrna Isoform Expression Specifically Correlates with Tumor Angiogenesis, Patient Survival, and Postoperative Relapse in Non-Small-Cell Lung Cancer

Abstract

Purpose: The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms ( VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non-small-cell lung cancer. Patients and Methods: We examined the expression of four different VEGF mRNA isoforms in 57 non- small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining. Results: All 57 lung cancer samples expressed the VEGF 121,VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P =. 013), short survival (< 24 months; P =.001), and early postoperative relapse (< 12 months; P =.001), Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P =.0001 and P =.0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence. Conclusion: The VEGF189 mRNA isoform expression ratio shows a greater correlation with turner angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF 165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with nonsmall-cell lung cancers. J Clin Oncol 19:432-441. (C) 2001 by American Society of Clinical Oncology.