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Updated: Jun 8, 2026

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Published on: November 5, 2020
Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient
Haruhisa Kitano1, Shun-Ichiro Kageyama, Stephen M Hewitt
1Laboratory of Pathology, Toyama University Hospital, Toyama, Japan.
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 positive for α-smooth muscle actin but negative for desmin, confirming a myofibroblasts phenotype. In contrast, myofibroblasts in inflammatory fibrotic lung diseases were podoplanin negative. Lymphatic vessel density was greater in the stromas with podoplanin expression than in the stroma lacking podoplanin-expressing stromal cells (P = .01). Survival data were available for non-small cell lung cancer. Stromal podoplanin expression was associated with poorer prognosis in adenocarcinoma (P < .001) and remains statistically significant after adjustment for sex, age, and stage (P = .01).
Conclusion:
Our data indicate that podoplanin expression in stromal myofibroblasts may function as a proangiogenic biomarker and may serve as a predictive marker of lymphatic/vascular spread of cancer cells and a prognostic marker of patient survival.