VEGF-C And CTTN Expression In Esophageal Squamous Cell Carcinoma And Its Clinical Significance

Background and Objective:Esophageal cancer as gastrointestinal tumor is a serious threat to our people’s health,and its incidence remains high in recent years. It is reported that in 2010, new cases of esophageal cancer is as high as 287,632, of which 90% are esophageal squamous cell carcinoma, according to the National Cancer Institute.The depth of tumor invasion and lymph node metastasis are considered as key factors to determine the clinical stage and the prognosis of patients with esophageal cancer, while frequent recurrence is reported in negative lymph node metastasis patients, lymphatic invasion is presumed culprit of recurrence,thus to find the crucial factors associated with lymph node metastasis especially lymphatic invasion has great significance of reducing the recurrence and improveing patients’ survival.Studies have shown that VEGF-C can promote the proliferation of tumor cell growth, invasion, metastasis and lymphangiogenesis, CTTN has close relations with tumor cell movement, invasion and anoikis capacity. But there was no study on the relation between VEGF-C、CTTN in esophageal squamous cell carcinoma with the pathological features of the depth of tumor invasion,lymphatic invasion and lymph node metastasis and prognosis in our country.To immunohistochemically investigate the clinicopathological role of expression of vascular endothelial growth factor C(VEGF-C),cortactin(CTTN) and lymphatic vessel invasion(LVI) detected by the D2-40 monoclonal antibody as well as whether their expression are independent predictors of the prognosis of esophageal squamous cell carcinoma.Methods:The present study immunohistochemically examined the expression of VEGF-C、cortactin(CTTN) and lymphatic vessel invasion(LVI) labled by D2-40 in 216 patients with esophageal squamous cell carcinoma(ESCC).Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed.Results:The positive rate of VRGF-C and CTTN in ESCC was 43.1%、63.9%, higher than 10.6%, 25.5% in adjacent normal tissue with significance(P<0.001); The total rate of LVI in 216 patients of ESCC is 63.9%. Positive expression of VEGF-C or CTTN was found to correlate significantly with depth of tumor invasion, TNM stage,lymph node metastasis and lymphatic invasion(P<0.001). To investigate the risk factor of lymph node metastasis, univariate and multivariate regression analyses were conducted to include age, gender, tumor size, histological grade, depth of invasion,VEGF-C, CTTN and lymphatic vessel invasion. Logistic regression analysis identified LVI, TNM stage,VEGF-C expression and CTTN expression(P=0.001,P=0.006,P =0.004,P=0.003,respectively) as both univariate and multivariable predictors of lymph node metastasis. Although univariate analysis showed that depth of tumor invasion was a statistically predictors of lymph node metastasis(p=0.042),this was not shown in multivariate analysis(P=0.056). The Kaplan-Meier analysis showed that the median overall survival of VEGF-C-positive patients was 28.0 months and that of the VEGF-C negative patients was 51.0 months with significance; the median overall survival of CTTN positive group was 26.0 months and that of the CTTN negative group was 54.0 months with significance as well. The LVI-positive group with the median overall survival of 26.0 months(95%CI:16.843~35.157 months) had significantly shorter survival than the LVI-negative group with that of patients with 54 months(95%CI:39.467~568.533 months). Cox multivariate analysis proved that TNM stage, VEGF expression,CTTN expression,LVI and lymph node metastasis were independent prognostic influence on overall survival.Conclusion:VEGF-C expression and CTTN expression,with the hope of a good marker to predict TNM stage,lymph node metastasis and lymphatic invasion, were independent prognostic factor in patients with ESCC.