Lymphangiogenesis in Esophageal Adenocarcinomas--Lymphatic Vessel Density as Prognostic Marker in Esophageal Adenocarcinoma

Abstract

We studied tumor lymphatic vascular density (LVD) as a predictive marker for the risk of lymph node (LN) metastasis and its relationship to other prognostic parameters and survival in 75 patients with esophageal adenocarcinoma. Samples were immunostained for D2-40, CD31, and vascular endothelial growth factor (VEGF). Microvessels were counted in densely vascular/lymphatic foci (hot spots) at x400 field (0.17 mm2). Intensity of staining for VEGF was scored on a 2-tiered scale. CD31 microvessel counts showed significant correlation with tumor stage and patient survival (P < .01). D2-40 LVD demonstrated a significant correlation with LN metastases, lymphovascular invasion, and tumor stage (r = 0.45, r = 0.47, and r = 0.37, respectively) and with shorter disease-free survival. D2-40 detected lymphovascular invasion in 29 of 75 cases, more than with CD31 (23/75) and H&E (18/75). VEGF was expressed in 48 (64%) of 75 cases and was significantly correlated with lymphovascular invasion, LN metastases, and overall survival. Our study showed that angiogenesis and lymphangiogenesis have important roles in the progression of esophageal adenocarcinoma.

THORACIC SURGERY Intratumoral lymphatic vessel density, and intratumoral and peritumoral lymphatic vessel invasion as predictive factors of lymph node metastasis and prognostic factors in esophageal cancer

“…We THORACIC SURGERY also found that the presence of both itLVI and ptLVI significantly correlated with tumor size, tumor depth, TNM stage, and residual tumor. Similar to our present results, Saad et al [21] and Imamura et al [17] showed a significant correlation between lymphatic invasion in the entire tumor tissue detected on D2-40 staining and depth of tumor invasion, stage, and lymph node metastases. Our analysis suggests that both itLVI and ptLVI promote malignant progression of esophageal cancer.…”

“…Our results showed that intratumoral lymphatic vessels were found in large tumors and in tumors that had already spread to regional lymph nodes. Several reports have shown that increased ptLVD is positively associated with prognostic factors, including lymph node metastasis in patients with gastric, and esophageal cancer [20,21]. This suggests that both high itLVD and high ptLVD have important roles in maintaining an appropriate environment for tumor cells and could enhance the entrance of tumor cells into lymphatic vessels by increasing the contact surface between lymphatic vessels and tumor cells.…”

“…Saad et al [21] showed that LVD correlated with a short disease-free survival. Inoue et al [16] and Imamura et al [17] found that high itLVD was significantly associated with worse overall survival in univariate analysis.…”

“…In esophageal adenocarcinoma, Saad et al [21] reported that LVD correlated significantly with LVI and lymph node metastases in multivariate analysis. On a prediction model of lymph node metastasis, Gockel et al [24] found that LVI only gained statistical significance in univariate analysis.…”

Associations between the expression of MTA1 and VEGF-C in esophageal squamous cell carcinoma with lymph angiogenesis and lymph node metastasis

“…It has previously been demonstrated that D2-40 was a lymphatic endothelial cell marker with high specificity, thus the present study used D2-40 to mark the lymphatic endothelial cells in ESCC and normal esophageal tissues, and to determine the LVD (17,18). The present study revealed that LVD was high in the tumor microenvironment surrounding ESCC, and were irregular in shape and exhibited the extended state.…”