Abstract:The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90-97) Key words: esophageal cancer, lymphatic vessel invasion, podoplanin, D2-40, lymph node metastasis, prognosis ageal cancer. More than 65% of patients with localized esophageal cancers and negative resection margin have a positive lymph node at the time of surgery [1]. However, despite complete tumor resection and extensive lymphadenectomy, systemic and local recurrence is common [2] and the five-year survival rate is 15-39% [3].The discovery over the last decade of markers of lymphatic endothelial cells like podoplanin (D2-40) [4], LYVE-1 [5] and Prox 1 [6], and the development of novel antibodies to these markers, have generated