Tissue microarray analysis reveals prognostic significance of syndecan-1 expression in prostate cancer.
BACKGROUND
Tissue microarrays (TMA) have recently emerged as powerful tools to rapidly analyze the clinical significance of new molecular markers in human tumors. Here, we have tested several molecular markers on a prostate TMA containing 637 different specimens.


METHODS
The specimens were from 551 patients with prostate cancer and long-term follow-up information on progression (median 5.3 years), tumor-specific and overall survival (median 5.9 years). Eighty-six specimens from benign prostatic hyperplasia were included as controls. Expression of Ki67, Bcl-2, p53, CD-10 (neutral endopeptidase), and syndecan-1 (CD-138) was analyzed by immunohistochemistry.


RESULTS
Gleason grade and Ki67 Labeling Index (LI) were independent predictors of early recurrence and poor survival. Bcl-2 predicted early recurrence, whereas p53 was associated with poor survival. Syndecan-1 overexpression also predicted early recurrence and was significantly associated with tumor specific survival, high Gleason grade, Ki67 LI, and Bcl-2 overexpression. Neoadjuvant hormonal therapy was associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10, but did not affect the expression of the remaining markers.


CONCLUSIONS
The results of this TMA study confirm a dominant prognostic significance of Gleason grading and Ki67 LI in prostate cancer, as compared to a less pronounced role of Bcl-2, and p53. We identified syndecan-1 as a new prognostic factor and provide evidence for an androgen-dependent regulation of CD-10 expression.
Zellweger
Tobias
T
Department of Urology, University of Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland.
Ninck
Christoph
C
Mirlacher
Martina
M
Annefeld
Matthias
M
Glass
Andrew G
AG
Gasser
Thomas C
TC
Mihatsch
Michael J
MJ
Gelmann
Edward P
EP
Bubendorf
Lukas
L
D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D015260:Neprilysin / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D040081:Protein Array Analysis / Q000379:methods; D011509:Proteoglycans / Q000096:biosynthesis*; D012189:Retrospective Studies; D053668:Syndecan-1; D053667:Syndecans; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D016159:Tumor Suppressor Protein p53; D015260:Neprilysin