Vascular endothelial growth factor‐C (VEGF‐C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder

Abstract

Purpose : It has been found that expression of vascular endothelial growth factor-C (VEGF-C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy. Methods : Eighty-seven patients who underwent radical cystectomy for clinically organ-confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF-C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined. Results : Vascular endothelial growth factor-C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor-C expression was significantly associated with the pathological T stage ( P = 0.0289), pelvic lymph node metastasis ( P < 0.0001), lymphatic involvement ( P = 0.0008), venous involvement ( P = 0.0002) and high MVD ( P = 0.0043). The multivariate analysis demonstrated that VEGF-C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF-C-positive tumors had significantly poorer prognoses than those with the VEGF-C-negative tumors ( P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age ( P = 0.0132) and pelvic lymph node metastasis ( P = 0.0333).Conclusion : The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

“…Among 1,384 genes that were regulated by BLACAT2 (P < 0.05, fold changes > 2.0), multiple genes that play critical roles in lymphatic metastasis, such as VEGF-C, SNAI2, and MMP9 (33)(34)(35), were significantly downregulated in BLACAT2-silenced cells ( Figure 5A). Furthermore, immunostaining and qPCR analyses revealed that the expression of VEGF-C, SNAI2, and MMP9, at both the mRNA and the protein levels, was increased in BLACAT2-transduced cells and decreased in BLACAT2-silenced cells ( Figure 5, B-D, and Supplemental Figure 13, A-E).…”

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

“…Therefore, expression and the processing status of VEGF-C and D in a given tissue appear to determine the lymphangiogenic and angiogenic activities of these growth factors [171]. Expression of VEGF-C in tumor tissue serves as a reliable marker for ongoing tumor lymphangiogenesis and increased risk of regional lymph node metastasis in many cancer types [172,173]. Data for VEGF-D are less consistent suggesting that its ability to promote metastatic spread via lymphatics depends on the investigated cancer type and/ or grade [174][175][176].…”

miR-128 downregulation promotes growth and metastasis of bladder cancer cells and involves VEGF-C upregulation

“…Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role (23). It was reported that the involvement of VEGF-C expression in the promotion of lymph node metastasis could be used as a decision-making biomarker for selected patients with invasive bladder cancer who underwent bladder-preserving radical surgery and were associated with an anti-apoptotic phenotype (24)(25)(26). RNA interference-mediated VEGF-C reduction suppresses malignant progression and enhances mitomycin C sensitivity of bladder cancer T24 cells (27).…”