A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma

Abstract

It has been widely demonstrated that neo-angiogenesis and its mediators (i.e. vascular endothelial growth factor), represent useful indicators of poor prognosis in non small cell lung carcinoma. In order to verify whether neovascularization and vascular endothelial growth factor may be considered useful markers of clinical outcome also in the small cell lung cancer subgroup, we retrospectively investigated a series of 75 patients with small cell lung carcinoma treated by surgery between 1980 and 1990. Immunohistochemically-detected microvessels and vascular endothelial growth factor expressing cells were significantly associated with poor prognosis, as well as with nodal status and pathological stage. In fact, patients whose tumours had vascular count and vascular endothelial growth factor expression higher than median value of the entire series (59 vessels per 0.74 mm 2 and 50% of positive cells, respectively), showed a shorter overall and disease-free survival ( P =0.001, P =0.001; P =0.008, P =0.03). Moreover, the presence of hilar and/or mediastinal nodal metastasis and advanced stage significantly affected overall and disease-free interval ( P =0.00009, P =0.00001; P =0.0001, P =0.00001). At multivariate analysis, only vascular endothelial growth factor expression retained its influence on overall survival ( P =0.001), suggesting that angiogenic phenomenon may have an important role in the clinical behaviour of this lung cancer subgroup. British Journal of Cancer (2002) 86 , 558–563. DOI: 10.1038/sj/bjc/6600130 www.bjcancer.com © 2002 Cancer Research UK

Production and upregulation of granulocyte chemotactic protein-2/CXCL6 by IL-1β and hypoxia in small cell lung cancer

“…Angiogenic factors have been extensively described in NSCLC but not in SCLC. Expression of VEGF was detected in 43 of 54 (81%) patients with SCLC, but was not associated with survival (Dowell et al, 2004) although increased expression of VEGF in SCLC was associated with poorer prognosis in another indepedent study (Fontanini et al, 2002). To date SCLC cells have been found to produce lower levels than NSCLC of pro-angiogenic factors such as VEGF and IL-8 (Yatsunami et al, 1997).…”

HIF-1α, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas

“…One of the most critical proangiogenic peptides induced by hypoxia is VEGF, and expression of VEGF correlates with poor prognosis in a number of human tumors (Ishigami et al, 1998;Fontanini et al, 2002). Cells were seeded in 12-well plates (0.25 Â 10 6 cells/well) and grown in complete media.…”

The Natural Progression of Microvasculature in Primary Tumor and Lymph Node Metastases in a Breast Carcinoma Model: Relationship between Microvessel Density, Vascular Endothelial Growth Factor Expression and Metastatic Invasion

“…A positive relationship between primary tumor microvessel density and risk of metastasis, tumor recurrence, and death has been widely observed [31][32][33][34][35] and high MVD in metastases is a negative prognostic factor. [36][37][38][39][40] There is, however, a paucity of studies comparing MVD in primary tumors and metastatic lesions. Since metastatic tumors are often less responsive to conventional chemotherapy than primary tumors, and microvasculature is critical for drug delivery to tumors, successful cancer therapy may require a better understanding of the differences in angiogenic microvasculature between metastases and primary tumors.…”