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


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).


CONCLUSIONS
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.
Kallakury
B V
BV
Department of Pathology and Laboratory Medicine, Albany Medical College, NY, USA.
Sheehan
C E
CE
Ambros
R A
RA
Fisher
H A
HA
Kaufman
R P
RP
Muraca
P J
PJ
Ross
J S
JS
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000601:surgery*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D015536:Down-Regulation; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011003:Ploidies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000601:surgery*
D018960:Hyaluronan Receptors; D018844:Cyclin-Dependent Kinases