Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma

Abstract

Vascular endothelial growth factor (VEGF) expression, vascularisation and tumour cell proliferation were analysed in 91 human epidermoid lung carcinomas using immunohistochemistry. A polyclonal anti-VEGF antibody was used for VEGF expression, a polyclonal antibody directed against human von Willebrand factor (factor VIII) to identify blood vessels and the proliferating cell nuclear antigen (PCNA) as a marker for proliferating cells. Positive staining for VEGF was obtained in 54 out of 91 cases (59%), the number of blood vessels varied from zero to 64 counts (mean 9.4) and the proportion of PCNA-positive cells varied from 1.3% to 72.1% (mean 25.2%). The mean PCNA labelling index and mean microvessel count in VEGF-positive tumours were significantly higher than those in VEGF-negative tumours (Wilcoxon rank sum test, P<0.0001; p<0.05). In addition, PCNA labelling index significantly increased with increasing VEGF expression (Jonckheere test, P<0.0001). In contrast, no association was found between PCNA labelling index and tumour vascularity (r=0.07, P=0.48). The close correlation of VEGF expression with tumour cell proliferation and microvessel density suggests that VEGF acts both as an autocrine growth factor and as stimulator for angiogenesis. However, tumour cell proliferation and microvessel growth and/or density may be regulated by separate mechanisms. Images Figure 1

Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression

“…Recently, Mattern et al (1996) analysed a series of 91 epidermoid lung carcinomas and, apart from the different percentage of cancers expressing the VEGF protein, they found a statistical association between the MC and VEGF expression. They did not analyse the relation between p53 and VEGF, which appears to be strictly connected in the regulation of tumour angiogenesis.…”

Vascular endothelial growth factor (VEGF) expression in prostatic tumours and its relationship to neuroendocrine cells

“…In this respect assays on breast tumours (Toi et al, 1994) and epidermoid lung carcinomas (Mattern et al, 1996) have demonstrated a correlation between VEGF expression and MVD measurements. Recent studies have indicated that measurement of intratumoral levels of VEGF may be useful in assessing the activity of tumour angiogenesis (Toi et al, 1996).…”

Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: correlation with clinicopathology and patient survival, and analysis of serum VEGF levels

“…VEGF has been reported to be synthesized and secreted by a variety of cultured tumour cells (Senger et al, 1986) and human solid tumours, such as brain tumours (Plate et al, 1992;Berkman et al, 1993;Samoto et al, 1995), lung cancers (Mattem et al, 1996), breast carcinomas , gastrointestinal tract adenocarcinomas (Brown et al, 1993a), renal and bladder carcinomas (Brown et al, 1993b;Takahashi et al, 1994) and epithelial ovarian carcinomas (Olson et al, 1994;Boocock et al, 1995;Abu-Jawdeh et al, 1996). Increased expression of VEGF has been suggested to be involved in tumorigenesis, metastasis and the production of malignant effusion via the enhancement of vascular permeability or angiogenesis Neufeld et al, al, 1994).…”