Vascular endothelial growth factor and lymph node metastasis in primary lung cancer

Abstract

Summary The relationship between vascular endothelial growth factor (VEGF) and lymph node metastasis was studied in 90 cases of primary lung cancer without distant metastasis. As a result of quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, the VEGF121 mRNA expression levels in lung cancer tissues with nodal metastasis (n = 35) were higher than in those without nodal metastasis (n = 55). However, no significant difference could be found in VEGF121 mRNA expression levels as stratified by tumour size (Ti NOMO vs T2NOMO). Simultaneously, ten lymph nodes (four node positive and six node negative) together with the corresponding primary lung tumours and adjacent normal lung tissue, were studied for VEGF expression. The VEGF mRNA expression in metastatic lymph nodes was intense in three out of the four cases examined. Further, while VEGF expression levels in metastatic lymph nodes were conspicuously higher than those for the primary site, all its expression levels in non-metastatic nodes were inferior to those of the primary tumours. Except for macrophages, the VEGF antigen was identified mainly in the cytoplasm of metastatic cancer cells and the endothelial cells of blood or lymphatic vessels in lymph nodes. Although the detailed mechanisms and the significance of strong VEGF expressions in metastatic lymph nodes are still unknown, these data are consistent with a model whereby VEGF increases the opportunity for nodal metastasis through neoblood and lymphatic vessels.

Expression of vascular endothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in oesophageal cancer

“…The pattern of VEGF is that VEGF expression of Group N(+) is much greater than that of Group N(-); however, the expression of VEGF is suppressed with the progression of metastatic stage. We and other investigators showed that over-expression of VEGF in primary tumours correlates with lymph node metastasis in oesophageal cancer and other tumours (Maeda et al, 1996;Moriyama et al, 1997;Ohta et al, 1997;Uchida et al, 1998). VEGF is a multifunctional molecule that has been implicated in vasculogenesis (Carmeliet et al, 1996;Ferrara et al, 1996), endothelial cell proliferation and migration (Senger et al, 1993), vascular permeability (Roberts and Palade, 1995), and stromal degradation through the activation of some proteolytic enzymes involved in tumour invasiveness and angiogenesis (Ferrara, 1996).…”

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts

“…Several reports indicated that expression of VEGF in tumor tissue of NSCLC significantly correlated with lymph node metastasis, tumor size, and advanced stage [10,15,16]. In terms of serum VEGF, Imoto et al [15] demonstrated that the elevated preoperative serum VEGF levels of patients who underwent complete tumor resection were significantly associated with advanced stage, suggesting the role of serum VEGF as an indicator of tumor burden.…”

“…It is a soluble dimeric 34-46 kDa protein which has been implicated in endothelial cell proliferation and migration, increased vascular permeability, and stromal degradation through the activation of proteolytic enzymes [2,[4][5][6]. VEGF expression has been demonstrated in a large variety of human malignancies including breast, lung, colorectal, bladder, and ovarian cancer [2,[6][7][8][9][10][11][12][13][14][15][16]. In non-small cell lung cancer (NSCLC), expression of VEGF has been reported in 50-95% of cases [8-10,12,14 -16].…”

“…In non-small cell lung cancer (NSCLC), expression of VEGF has been reported in 50-95% of cases [8-10,12,14 -16]. Several studies have suggested that expression of VEGF in NSCLC correlates with poor prognosis, lymph nodes metastasis and microvessel count [8,10,12,[14][15][16]. Angiogenesis might play an important role in the progression of NSCLC in which metastasis to regional lymph nodes and distant organs are frequent events [17].…”

Quantification of VEGF mRNA Expression in Non-Small Cell Lung Cancer Using a Real-Time Quantitative Reverse Transcription-PCR Assay and a Comparison with Quantitative Competitive Reverse Transcription-PCR

“…It is therefore important to be able to assess VEGF gene product expression in tumor cells in order to understand the role of VEGF in tumor angiogenesis and in the biological behavior of tumors. Many studies of VEGF expression in various malignancies have been performed in recent years (Berkman et al, 1993;Boocock et, 1995;Fontanini et al, 1997;Ohta et al, 1996Ohta et al, , 1997Oshika et al, 1994;Suzuki et al, 1996;Tokunaga et al, 1998;Viglietto et al, 1996).…”