Overexpression of vascular endothelial growth factor and its receptors in bronchial dypslasia demonstrated by quantitative RT-PCR analysis.
Neoangiogenesis is required for the growth of invasive lung carcinoma, however, the role of angiogenesis in the progression of premalignant changes to carcinoma of the lung is less clear. We have evaluated vascular endothelial growth factor (VEGF) expression and microvessel densities (MVDs) in 62 bronchoscopic biopsies from normal, reactive (basal cell hyperplasia (BCH)) and dysplastic bronchial epithelium and in tissue from twenty-seven invasive lung carcinomas in an effort to demonstrate angiogenic activity in these preneoplastic lesions and determine whether it is associated with increased bronchial epithelial VEGF expression. MVDs and VEGF RNA expression measured by quantitative RT-PCR were found to be elevated in comparison to normal bronchial tissue in bronchial dysplasias and invasive lung carcinomas but not in basal cell hyperplasias. Immunohistochemical (IHC) analyses revealed that expression of VEGF arose predominantly from bronchial epithelium. ELISA analysis of lung tumor tissue showed that elevated VEGF protein expression correlated with VEGF RNA levels (r=0.59, p=0.004). Increased expression of VEGF RNA was also found in histologically normal bronchial mucosa from patients with either dysplasia at other sites or a history of heavy tobacco use suggesting a possible field effect in regard to the elaboration of VEGF. Furthermore, analysis of VEGF isoforms and VEGF receptors by semi-quantitative RT-PCR in dysplastic and invasive lesions revealed characteristic altered patterns of expression in dysplasia and early cancer as compared to normal tissue. These results indicate that angiogenesis develops early in lung carcinogenesis and is associated with overexpression of VEGF.
Merrick
Daniel T
DT
Department of Pathology, Denver Veteran's Affairs Medical Center, 1055 Clermont St., Denver, CO 80220, USA. Daniel.Merrick@med.va.gov
Haney
Jerry
J
Petrunich
Sheila
S
Sugita
Michio
M
Miller
York E
YE
Keith
Robert L
RL
Kennedy
Tim C
TC
Franklin
Wilbur A
WA
D001706:Biopsy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D011230:Precancerous Conditions / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D040262:Receptors, Vascular Endothelial Growth Factor