Enzyme histochemical analysis of lymphatic vessels in colon carcinoma: occurrence of lymphangiogenesis within the tumor

Abstract

Background/aims: While it is generally recognized that the lymph vessel is absent in solid carcinoma, a few papers have reported the presence of intratumoral lymph vessels. The present study was carried out to clarify whether or not intratumoral lymphangiogenesis occurs.

Methodology: To identify lymphatics in colon carcinomas, tumor-adjoining and normal submucosa, we tried using an enzymatic histochemistry procedure to examine the specific high activity of 5'-nucleotidase that is seen in lymphatic endothelial cells. Additionally, arterioles and venules were identified by alkaline phosphatase and dipeptidyl (amino) peptidase IV staining, respectively.

Results: Intratumoral lymphatic vessels were observed in 30 of 34 colon carcinomas (91%), and arterioles were found in all cases. However, no venules were identified within the tumor. The lymphatic density (mean +/- SD vessels/mm2) increased in the order of the submucosa near the tumor (21.9 +/- 9.5), normal submucosa (27.9 +/- 13.8) and tumor tissue (33.9 +/- 25.1). Intratumoral lymphatic density was significantly higher than that in the submucosa near the tumor (P<0.05). Intratumoral lymphatic density is related to arteriolar density (r=0.284, P=0.0012). The ratio of lymphatic/arteriolar density in the tumor was significantly higher than that seen in the submucosa near the tumor (0.78 +/- 0.76 vs. 0.51 +/- 0.36, P<0.05). Intratumoral lymphatic density was relatively higher in cases with lymph node metastasis than in those without metastasis, but was not related to tumor size, depth of tumor invasion, distant metastasis and TNM stage.

Conclusions: Enzyme histochemistry revealed active lymphangiogenesis and the absence of venules within the tumor. Intratumoral lymphatic density was relatively correlated to arteriolar density. Enzyme histochemistry is a simple and quickly processed method that can be used to differentiate lymphatics from arterioles and venules.