Podoplanin expression in cancer-associated fibroblasts predicts aggressive behavior in melanoma

J Cutan Pathol. 2014 Jul;41(7):561-7. doi: 10.1111/cup.12322. Epub 2014 Apr 9.

Abstract

Background: Recent studies have showed podoplanin expression in several tumors, which has been associated with lymph node metastasis and poor prognosis. Podoplanin expression in cancer-associated fibroblasts also correlates with tumor progression. However, the association of podoplanin expression with melanomas remains unclear.

Methods: To clarify the prognostic significance of podoplanin in melanoma, podoplanin expression in tumor cells and cancer-associated fibroblasts was examined by immunohistochemistry in tissue samples collected from 55 melanoma patients.

Results: Podoplanin expression in tumor cells was identified in 38 patients (69.1%) but did not show correlation with characteristics of tumor progression such as tumor thickness (p = 0.52) and sentinel lymph node (SLN) metastasis (p = 0.79). Podoplanin expression in cancer-associated fibroblasts was observed in 25 patients (45.5%), 11 of whom (44.0%) had SLN metastasis. In contrast, only 4 of 30 patients (13.3%) with podoplanin-negative cancer-associated fibroblasts exhibited SLN metastasis. Podoplanin-positive cancer-associated fibroblasts were associated with increased tumor thickness and SLN metastasis. Furthermore, patients with podoplanin-positive cancer-associated fibroblasts had poorer survival than those with podoplanin-negative cancer-associated fibroblasts (p = 0.0148).

Conclusion: The presence of podoplanin expression in cancer-associated fibroblasts correlates with aggressive behavior in melanoma and might therefore serve as a useful prognostic factor for patients with melanoma.

Keywords: cancer-associated fibroblasts; melanoma; metastasis; podoplanin; prognostic factor.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Disease-Free Survival
  • Female
  • Fibroblasts* / metabolism
  • Fibroblasts* / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Melanoma* / metabolism
  • Melanoma* / mortality
  • Melanoma* / pathology
  • Membrane Glycoproteins / biosynthesis*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Retrospective Studies
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology
  • Survival Rate

Substances

  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PDPN protein, human