Podoplanin Expression in Cancerous Stroma Induces Lymphangiogenesis and Predicts Lymphatic Spread and Patient Survival

Abstract Context.—Podoplanin is a mucin-type glycoprotein and a lymphatic endothelial marker. Immunohistochemical staining for podoplanin is currently used as a routine pathologic diagnosis tool in Japan to identify lymphatic invasion of cancer cells. Recent reports suggest that podoplanin and other proangiogenic molecules are expressed in stromal fibroblasts and myofibroblasts. Objective.—To analyze the distribution of podoplanin expression in tumor stroma and its clinical and biologic significance. Design.—We performed immunohistochemistry for podoplanin on tissue microarrays from 1350 cases of 14 common cancer types. Results.—Two hundred eighty-seven of 662 cases (43%) showed podoplanin expression in the stromal cells within cancer nests. Stromal podoplanin expression in 14 common cancer types was significantly associated with tumor stage (P < .001), lymph node metastases (P < .001), lymphatic invasion (P  =  .02), and venous invasion (P < .001). The stromal cells positive for podoplanin were also posi...