Correlation of p34cdc2 cyclin-dependent kinase overexpression, CD44s downregulation, and HER-2/neu oncogene amplification with recurrence in prostatic adenocarcinomas

J Clin Oncol. 1998 Apr;16(4):1302-9. doi: 10.1200/JCO.1998.16.4.1302.

Abstract

Purpose: To test whether p34cdc2 overexpression, CD44s downregulation, and HER-2/neu amplification correlate with disease recurrence after radical prostatectomy, and to evaluate a possible biologic association between p34cdc2 and HER-2/neu expression.

Materials and methods: Immunohistochemical (IHC) detection of both p34cdc2 cyclin-dependent kinase (CDK) and CD44s expression and fluorescence in situ hybridization (FISH)-based analysis of HER-2/neu gene status were performed on formalin-fixed, paraffin-embedded sections of 106 prostatic adenocarcinomas (PACs). Findings were correlated with Gleason grade, pathologic stage, DNA ploidy, and postsurgical biochemical disease recurrence.

Results: CDK overexpression correlated with tumor grade (P = .001), DNA ploidy (P = .001), pathologic stage (P = .04), and disease recurrence (P = .01). CD44s downregulation correlated with grade (P = .03), ploidy (P = .01), and recurrence (P = .02). HER-2/neu amplification correlated with grade (P = .001), ploidy (P = .001), and recurrence (P = .01). On multivariate analysis, CDK overexpression independently predicted recurrence (P = .001) after prostatectomy. CDK expression correlated with HER-2/neu status with 32 of 65 (49%) tumors that overexpressed CDK and showed concomitant HER-2/neu amplification (P = .04).

Conclusion: This study showed that p34cdc2, CD44s, and HER-2/neu are variably expressed or amplified in prostatic carcinoma and that such alteration may affect tumor behavior. In addition, CDK overexpression and HER-2/neu amplification may be biologically related.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery*
  • Cyclin-Dependent Kinases / metabolism*
  • Down-Regulation
  • Gene Amplification
  • Genes, erbB-2 / genetics*
  • Humans
  • Hyaluronan Receptors / metabolism*
  • In Situ Hybridization, Fluorescence
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Ploidies
  • Prostatectomy
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery*

Substances

  • Hyaluronan Receptors
  • Cyclin-Dependent Kinases