Characterization of reactive stroma in prostate cancer: involvement of growth factors, metalloproteinase matrix, sexual hormones receptors and prostatic stem cells

Int Braz J Urol. 2015 Sep-Oct;41(5):849-58. doi: 10.1590/S1677-5538.IBJU.2014.0355.

Abstract

Introduction and objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells.

Materials and methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: a-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Era and ERß.

Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERa.

Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Adenocarcinoma / chemistry
  • Adenocarcinoma / pathology*
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / analysis
  • Biomarkers, Tumor / analysis
  • DNA-Binding Proteins / analysis
  • Disease Progression
  • Epithelial Cells / chemistry
  • Epithelial Cells / pathology*
  • Estrogen Receptor alpha / analysis
  • Fibroblast Growth Factor 2 / analysis
  • GPI-Linked Proteins / analysis
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Matrix Metalloproteinase 2 / analysis
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / analysis
  • Neoplastic Stem Cells / chemistry
  • Neoplastic Stem Cells / pathology*
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / pathology*
  • Stromal Cells / chemistry
  • Stromal Cells / pathology*
  • Transcription Factors / analysis
  • Tumor Microenvironment
  • Vimentin / analysis

Substances

  • Actins
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Estrogen Receptor alpha
  • GPI-Linked Proteins
  • MYCBP protein, human
  • Neoplasm Proteins
  • PSCA protein, human
  • Transcription Factors
  • Vimentin
  • Fibroblast Growth Factor 2
  • Insulin-Like Growth Factor I
  • Matrix Metalloproteinase 2