Fibroblast as a critical stromal cell type determining prognosis in prostate cancer

Prostate. 2019 Sep;79(13):1505-1513. doi: 10.1002/pros.23867. Epub 2019 Jul 3.

Abstract

Background: Tumor stroma associates with prostate cancer (PCa) progression, but its specific cellular composition and association to patient survival outcome have not been characterized.

Methods: We analyzed stromal composition in human PCa using multiplex immunohistochemistry and quantitative, high-resolution image analysis in two retrospective, formalin-fixed paraffin embedded observational clinical cohorts (Cohort I, n = 117; Cohort II, n = 340) using PCa-specific mortality as outcome measurement.

Results: A high proportion of fibroblasts associated with aggressive disease and castration-resistant prostate cancer (CRPC). In a multivariate analysis, increase in fibroblast proportion predicted poor cancer-specific outcome independently in the two clinical cohorts studied.

Conclusions: Fibroblasts were the most important cell type in determining prognosis in PCa and associated with CRPC. Thus, the stromal composition could be critically important in developing diagnostic and therapeutic approaches to aggressive prostate cancer.

Keywords: castration-resistant prostate cancer; digital image analysis; multiplex tissue imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology*
  • Cohort Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Prognosis
  • Proportional Hazards Models
  • Prostatectomy
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Prostatic Neoplasms, Castration-Resistant / surgery
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Vimentin / biosynthesis

Substances

  • VIM protein, human
  • Vimentin