Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer

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 clinicopath ologic characteristics, tumor angiogenesis, and outcome of patients with no n-small-cell lung cancer. Patients and Methods: We examined the expression of four different VEGF mRN A isoforms in 57 non-small-cell lung cancers using reverse transcriptase po lymerase chain reaction and the tumor angiogenesis using immunohistochemica l staining. Results: All 57 lung cancer samples expressed the VEGF 121,VEGF165, and VEG F189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tu moral VEGF189 mRNA isoform expression ratio was associated with a high intr atumoral microvessel count (P =.013), short survival (< 24 months; P =.001) , and early postoperative relapse (< 12 months; P =.001), Survival and post operative relapse time were significantly shorter in patients with a high c ompared with a low tumor VEGF189 mRNA isoform expression ratio (P =.0001 an d 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 mon ths) and early relapse (< 12 months). Multivariate analysis showed that VEG F 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and pos toperation recurrence. Conclusion: The VEGF189 mRNA isoform expression ratio shows a greater corre lation with turner angiogenesis, postoperative relapse time, and survival t han do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA iso forms 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.