Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival

Arch Pathol Lab Med. 2010 Oct;134(10):1520-7. doi: 10.1043/2009-0114-OA.1.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Age Factors
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphangiogenesis
  • Lymphatic Metastasis
  • Male
  • Membrane Glycoproteins / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Predictive Value of Tests
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Protein Array Analysis / methods
  • Stromal Cells / pathology*
  • Survival Rate

Substances

  • Membrane Glycoproteins
  • PDPN protein, human