Clinical significance of VEGF-C and VEGFR-3 expression in non-small cell lung cancer

Abstract

The relationship between vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor 3 (VEGFR-3) expression and clinicopathologic features of the patients with non-small cell lung cancer (NSCLC) was investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3 expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3 were highly expressed in cytoplasm and membrane in lung cancer tissues with the positive rate being 55.4 % and 52.3 % respectively, while there was no expression in the normal lung tissues. The expression of VEGF-C was significantly increased in adenocacinoma as compared to other types of NSCLC (P<0.05). The VEGFR-3 expression was closely related with lymph node metastasis (P<0.01) and TNM stage (P<0.05). There was a positive correlation between the VEGF-C and VEGFR-3 expression in NSCLC patients (r=0.658, P<0.01). It is suggested that VEGFR-3 plays an important role in the lymphatic metastasis of NSCLC. The interaction between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer metastasis.

Clinical significance of vascular endothelial growth factor‐C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma

“…Several studies have reported VEGF-C expression in NSCLCs. [17][18][19][20][21][22] In addition, NSCLC patients with nodal metastasis revealed higher serum VEGF-C levels than those without. 31 However, the association of tumor-cell VEGF-C and nodal metastasis in NSCLCs is still debated.…”

“…31 However, the association of tumor-cell VEGF-C and nodal metastasis in NSCLCs is still debated. Three studies reported positive associations of tumor-cell VEGF-C status with nodal metastasis in NSCLCs 17,18 and micrometastasis in Stage I NSCLCs. 19 In contrast, three studies described no association of tumor-cell VEGF-C status with nodal metastasis in NSCLCs.…”

“…15,16 However, an association of VEGF-C with nodal metastasis is still unclear in patients with nonsmall cell lung carcinoma (NSCLC). [17][18][19][20][21][22] Niki and coworkers 23 described low VEGF-D mRNA levels in tumor tissue samples of lung adenocarcinoma patients with lymph node metastasis, although these samples showed high mRNA levels of VEGF, VEGF-B, and VEGF-C. VEGFR-3 expression was observed in blood and lymphatic vessels in stroma of various malignancies 24 -26 including NSCLCs. 17,18,20,27,28 However, there has been no report to assess the clinicopathologic significance of VEGF-C and VEGFR-3 in patients with TNM classification T1 lung adenocarcinoma (tumor size of Յ 3 cm less in diameter).…”

“…[17][18][19][20][21][22] Niki and coworkers 23 described low VEGF-D mRNA levels in tumor tissue samples of lung adenocarcinoma patients with lymph node metastasis, although these samples showed high mRNA levels of VEGF, VEGF-B, and VEGF-C. VEGFR-3 expression was observed in blood and lymphatic vessels in stroma of various malignancies 24 -26 including NSCLCs. 17,18,20,27,28 However, there has been no report to assess the clinicopathologic significance of VEGF-C and VEGFR-3 in patients with TNM classification T1 lung adenocarcinoma (tumor size of Յ 3 cm less in diameter). To statistically analyze clinocopathologic implications of VEGF-C and its receptor, VEGFR-3, in patients with T1 lung adenocarcinoma, the current study immunohistochemically examined VEGF-C and VEGFR-3 in T1 lung adenocarcinomas and compared their expression with VEGF expression and the density of microvessels, mast cells, and macrophages in cancerous stroma.…”

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

“…VEGF-C can also attract macrophages [124] that can alter the tumor microenvironment to promote invasion. Furthermore, some tumor cells also express VEGFR-3 and thus may benefit from autocrine signaling of VEGF-C or -D [121,[125][126][127][128][129]. Such autocrine signaling could help tumor cells home to lymphatics by guiding them in the direction of flow [42].…”