Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer

Prostate. 2012 Feb 1;72(2):201-8. doi: 10.1002/pros.21422. Epub 2011 May 11.

Abstract

Background: c-Fes is a proto-oncogene encoded non-receptor protein-tyrosine kinase (PTK). However, genetic studies have indicated that it has anti-tumorigenic effects in certain cancers. The pathological and clinical significance of c-Fes in prostate cancer are unknown.

Methods: Expression of c-Fes was evaluated in normal glands, prostatic intraepithelial neoplasia (PIN), cancer cells in tissues of knock-in mouse adenocarcinoma prostate (KIMAP) model, and prostate cancer patients free of metastasis. Expression of c-Fes was analyzed by immunohistochemistry, and quantified by using the immunoreactivity score (IRS) (staining intensity × percentage of positive cells). Relationships between c-Fes expression and pT stage, Gleason's score (GS), and biochemical recurrence in patients who underwent radical surgery were also investigated.

Results: In KIMAP, the percentage in normal glands, PIN and cancer cells positive for c-Fes expression were 0 (0/7), 25.0 (2/8), and 100% (7/7), respectively. In human tissues, c-Fes expression was also significantly higher in cancer cells than in normal cells and PIN, and it correlated with pT stage (P < 0.001) and GS (P = 0.047). Multivariate analysis showed that c-Fes expression was an independent predictor of poor outcome poor prognosis (hazard ratio = 3.21, 95% confidence interval = 1.11-9.37, P = 0.032).

Conclusion: The results suggested that c-Fes expression is a useful predictor of biochemical recurrence after radical surgery. The results also suggested that c-Fes is a potentially useful therapeutic target in prostate cancer and a predictor of biochemical recurrence after radical prostatectomy.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Animals
  • Disease Models, Animal
  • Disease-Free Survival
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Predictive Value of Tests
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-fes / biosynthesis*
  • Proto-Oncogene Proteins c-fes / genetics
  • Retrospective Studies

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • FES protein, human
  • Proto-Oncogene Proteins c-fes