Prognostic significance of HER-2/neu gene amplification status by fluorescence in situ hybridization of prostate carcinoma.
BACKGROUND
HER-2/neu gene amplification, established as a prognostic factor in breast carcinoma and other cancers, has not been correlated with outcome in prostate carcinomas (PCs).


METHODS
HER-2/neu gene amplification was determined by automated fluorescence in situ hybridization (FISH) using a unique sequence cosmid probe on 113 formalin fixed, paraffin embedded 4-microns tissue sections and the results compared with tumor grade, DNA ploidy, HER-2/neu protein expression by immunohistochemistry (IHC), serum prostate specific antigen, pathologic stage, and postoperative disease recurrence (mean follow-up of 44 months).


RESULTS
HER-2/neu gene amplification by FISH (41% of PCs) correlated with tumor grade (P = 0.001) and DNA ploidy status (P = 0.0003). HER-2/neu protein overexpression by IHC (29% of PCs) correlated with grade (P = 0.03), but not with DNA ploidy. A trend for similar HER-2/neu status in each PC by IHC and FISH did not reach statistical significance (P = 0.25). On univariate analysis, HER-2/neu amplification by FISH (P = 0.029), tumor grade (P = 0.013), and DNA ploidy (P = 0.016) correlated with postoperative disease recurrence. HER-2/neu expression by IHC did not correlate with outcome. On multivariate analysis, grade (P = 0.0001) and ploidy (P = 0.001) were independent outcome predictors; HER-2/neu amplification by FISH reached near-independent significance (P = 0.125).


CONCLUSIONS
HER-2/neu gene amplification by FISH on archival PCs significantly correlates with grade and DNA ploidy status, is more sensitive than IHC in detecting HER-2/neu gene abnormalities, predicts postoperative disease recurrence, and may prove important in planning therapy for patients with prostate carcinoma.
Ross
J S
JS
Department of Pathology and Laboratory Medicine, Albany Medical College, New York 12208, USA.
Sheehan
C E
CE
Hayner-Buchan
A M
AM
Ambros
R A
RA
Kallakury
B V
BV
Kaufman
R P
RP
Fisher
H A
HA
Rifkin
M D
MD
Muraca
P J
PJ
D000230:Adenocarcinoma / Q000145:classification / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics
D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases