CCR7 and VEGF-C: molecular indicator of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy?

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with a high incidence of lymph node metastasis. This study was undertaken to investigate the expression of CCR7 and VEGF-C in pN0 ESCC and its relationship with lymphatic metastatic recurrence.

METHODS

The expression of CCR7 and VEGF-C was examined by RT-PCR and immunohistochemistry. The recurrence rates were calculated by the Kaplan-Meier method and their difference was determined by log rank analysis. Cox regression analysis was performed to determine the independent risk factors.

RESULTS

In 99 patients, CCR7 mRNA expression was observed in 42 patients with a 3 year recurrence rate of 57.1%; VEGF-C mRNA expression was observed in 52 patients with a 3 year recurrence rate of 53.8%; and coexpression of CCR7 mRNA and VEGF-C mRNA was observed in 22 patients with a 3 year recurrence of 63.6%. Neither CCR7 mRNA nor VEGF-C mRNA expression was observed in 27 patients with a 3 year recurrence rate of 22.2%. The recurrence rates of patients with positive expression of CCR7 mRNA and/or VEGF-C mRNA were significantly higher than in patients without expression of both CCR7 mRNA and VEGF-C mRNA. We achieved better concordance between RT-PCR and immunohistochemistry detection of both markers. The Cox regression analysis showed tumor T classification, positive expression of CCR7/VEGF-C mRNA, and positive expression of CCR7/VEGF-C protein in tumor tissues to be independent risk factors for 3 year recurrence.

CONCLUSIONS

Patients with positive expression of CCR7 and/or VEGF-C have a higher recurrence rate than patients without expression of both CCR7 and VEGF-C. CCR7 and VEGF-C may become molecular indicators of disease in patients vulnerable to lymphatic metastatic recurrence.