Journal of Clinical Oncology, Vol 16, 1302-1309, Copyright © 1998 by American Society of Clinical Oncology
Correlation of p34cdc2 cyclin-dependent kinase overexpression, CD44s downregulation, and HER-2/neu oncogene amplification with recurrence in prostatic adenocarcinomas
BV Kallakury, CE Sheehan, RA Ambros, HA Fisher, RP Kaufman Jr, PJ Muraca and JS Ross
Department of Pathology and Laboratory Medicine, Albany Medical College, NY, USA.
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.
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