The changes of angiogenesis and immune cell infiltration in the intra- and peri-tumoral melanoma microenvironment

Int J Mol Sci. 2015 Apr 9;16(4):7876-89. doi: 10.3390/ijms16047876.

Abstract

Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups--pT1 (35), pT2 (17), pT3 (18) and pT4 (12)--and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Melanoma / blood supply*
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Microvessels / metabolism
  • Microvessels / physiopathology
  • Middle Aged
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology*
  • Skin Neoplasms / blood supply*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Thy-1 Antigens / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Thy-1 Antigens