Podoplanin expression in advanced-stage gastric carcinoma and prognostic value of lymphatic microvessel density

In gastric cancer, lymph node metastasis is a major prognostic factor. Tumor lymphangiogenesis promotes metastasis in experimental models, but in human tumors data about the presence and clinical significance of lymphatic vessels in the tumor area are controversial. We investigated 70 patients with advanced-stage gastric carcinoma and the pathological examination showed 40 cases with intestinal subtype and 30 cases with diffuse subtype. Forty three from 70 cases had regional lymph node metastasis. Additional slides were stained with an antibody against podoplanin, and lymphatic microvessel density (LMVD) was evaluated in the tumoral and peritumoral areas. Lymphatic vessels were identified in tumor area in all cases and LMVD was higher in the peritumoral than in the tumor area. Podoplanin-positive vessels in tumor area were usually small, with narrow lumen. A significant correlation was found between LMVD and stage of the tumor (p<0.002) and lymph node metastasis (p<0.031), but not with the pathological subtype and grade of the tumor. We found tumor cells in the lumen of lymphatic vessels in 11 cases, whereas tumor cells expressing podoplanin were found in 4 cases of less differentiated diffuse subtype gastric carcinoma. In conclusion, our results suggest that LMVD predicts tumor stage and lymph node metastasis, and podoplanin-positive tumor cells select a subgroup of tumors with high potential of invasion and metastasis.