Angiogenesis correlates with vascular endothelial growth factor expression but not with Ki-ras oncogene activation in non-small cell lung carcinoma.
A total of 195 non-small cell lung carcinoma (NSCLC) specimens were studied for the presence of mutations in their ras family genes, for tumor vascularity, and for their immunostaining pattern with an antibody to vascular endothelial growth factor (VEGF). ras mutation was found in 37 of 104 (34.6%) adenocarcinoma specimens, in 0 of 64 squamous cell carcinomas, and in 2 of 27 (7.4%) large cell undifferentiated carcinomas. All mutations were found on the Ki-ras gene, with 37 (95%) of them on codon 12 and the remaining 2 on codon 13. Thirty (77%) of the mutations were G to T transversions. There was a correlation between increasing tumor vascularity and VEGF immunostaining score, but there was no correlation between either of them with the activation of the ras oncogene. A study of VEGF mRNA expression in 14 NSCLC cell lines also demonstrated a lack of correlation between the constitutive expression levels of VEGF and the presence or absence of ras mutation in these cell lines. The results suggest that VEGF is a major angiogenesis factor in NSCLC but that other factors beside ras mutations may influence tumor vascularity in these tumors. The two parameters may potentially serve as independent prognostic factors in NSCLC.
Tsao
M S
MS
Departments of Pathology, Ontario Cancer Institute/Princess Margaret Comprehensive Cancer Center-Toronto Hospital and University of Toronto, Ontario, M5G 2M9.
Liu
N
N
Nicklee
T
T
Shepherd
F
F
Viallet
J
J
D000483:Alleles; D001980:Bronchi / Q000166:cytology; D002196:Capillaries / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000235:genetics / Q000503:physiopathology; D002461:Cell Line, Transformed; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004273:DNA, Neoplasm; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)