Decreased expression of Cyr61 is associated with prostate cancer recurrence after surgical treatment

Clin Cancer Res. 2010 Dec 1;16(23):5908-13. doi: 10.1158/1078-0432.CCR-10-1200.

Abstract

Purpose: Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. Previous studies have suggested that Cyr61 may be a marker for a more aggressive phenotype. In this study, we evaluated the association between Cyr61 staining intensity and subsequent recurrence after surgical treatment of clinically localized prostate cancer.

Experimental design: A study of 229 men with recurrence and 229 controls matched on age, race, pathologic stage, and Gleason sum nested in a cohort of men who underwent radical prostatectomy for clinically localized prostate cancer, utilizing immunohistochemistry analysis of tissue microarray (TMA) sections, was conducted. Odds ratios (OR) of recurrence and 95% confidence intervals (CIs) were estimated using conditional logistic regression.

Results: Recurrence was identified in 12.2% of cases, and in 24.0% of controls that had at least 1 TMA spot containing cancer with a staining intensity of 3 (P = 0.001). Taking into account age, pathologic stage and grade, presurgery prostate-specific antigen concentration, and calendar of surgery as a measure of tissue block storage time, men with a Cyr61 staining intensity of 3 were 56% less likely to recur than men with a lower staining intensity (OR = 0.44, 95% CI = 0.22-0.90).

Conclusions: High Cyr61 staining intensity in adenocarcinoma was associated with a lower risk of recurrence after surgical treatment of prostate cancer independent of pathologic tumor characteristics. If validated in other sample sets, Cyr61 may serve as a tissue biomarker for stratifying men for risk of recurrence and thus could inform treatment decision making.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cohort Studies
  • Cysteine-Rich Protein 61 / metabolism*
  • Down-Regulation / physiology
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prostatectomy / methods
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery*
  • Recurrence
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Cysteine-Rich Protein 61