Over-expression of both VEGF-C and Twist predicts poor prognosis in human breast cancer.

BACKGROUND: Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis. METHODS: The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated. RESULTS: Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (P = 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (P = 0.001) and overall survival, OS (P = 0.011). CONCLUSIONS: Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.

Downregulated ECRG4 is correlated with lymph node metastasis and predicts poor outcome for nasopharyngeal carcinoma patients.

OBJECTIVE: Esophageal cancer-related gene 4 (ECRG4) is a new candidate tumor suppressor gene. In this retrospective study, we evaluated ECRG4 protein expression in patients with nasopharyngeal carcinoma (NPC) under curative treatment and examined its association with pathological features and clinical outcomes as a possible biomarker for diagnosis and prognosis of NPC. METHODS: We enrolled 122 patients with a first diagnosis between January 2001 and December 2003. Tumor tissue and control tissue from biopsies underwent immunohistochemical staining for ECRG4. ECRG4 expression was analyzed by clinicopathological variables. After Kaplan-Meier survival analysis, we used Cox proportional hazards regression to estimate the predictive effect of ECRG4 expression on overall survival. RESULTS: ECRG4 protein level was lower in NPC than control tissue (P < 0.01). It was inversely related to node status (P < 0.001) and clinical stage (P = 0.027). ECRG4 expression was associated with overall survival, and downregulated ECRG4 expression was an independent prognostic factor of poor survival (hazard ratio = 0.677, 95 % confidence interval 0.463-0.989, P = 0.044). CONCLUSIONS: A significant NPC patients showed downregulated ECRG4 expression, which is correlated with lymph node metastasis. The marker could be an independent prognostic factor for NPC patients. The precise function of ECRG4 in the progression of NPC, especially for lymphatic metastasis, deserves further investigation, which would bring a new target for personalized therapy.