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transcribed into cDNA. Primers and Taq-Man probes for the cDNA-specific real-time quantitative PCR assay were designedfor the four molecular markers understudy and GAPDH. The level of GAPDHexpression was measured in all samples tonormalize for sample-to-sample differencesin RNA input, quality and reverse tran-scription efficiency.Results: Of the 96 patients studied, histo-logical diagnosis was BPH in 26 (27.1%),BPH and prostatitis in 45 (46.9%) andprostate cancer in 25 (26%) respectively.All samples were positive for the four mo-lecular markers. Real-time PCR measure-ments of mRNA levels showed that themean �/- SD of the relative expression forpatients with prostate cancer compared tothose with BPH and prostatitis was signifi-cantly higher for AMACR (p� 0.002),EZH2 (p�0.03); significantly lower forHer2/neu (p�0.01) and not significantlydifferent for survivin (p�0.55). Patientswith high grade prostate intraepithelialneoplasia (PIN) had higher AMACR(p�0.001) and EZH2 (p� 0.001) expres-sion ratios compared with survivin (NS)and Her2/neu (NS).Conclusions: These data demonstratethat AMACR, EZH2 and Her2/neu expres-sion in primary lesions of the prostate arenot affected by the presence of varyinggrades of inflammation of the prostate andcan therefore be important predictivemarkers of prostate cancer aggressiveness.
POD-5.10Endothelin-1 Immunostaining as aPrognostic Marker of pT3aAdenocarcinoma on Prostate BiopsiesMenard J1, Perez T1, Joseph K2,Birembaut P2, Staerman F1
1Department of Urology and Andrology,CHU Reims, Reims, France; 2Departmentof Pathology, CHU Reims, Reims, France
Introduction and Objectives: To evalu-ate immunohistochemical expression ofendothelin-1 (ET-1) as a prognostic markerof pT3a prostate cancer on prostate biop-sies. We compared pathological data andET-1 immunostaining on biopsies andprostate surgical specimen between pT2and pT3a tumors.Material and Methods: Sixty-eight radi-cal prostatectomies (RP) were realized forclinically localised prostate cancer diag-nosed on needle biopsies (35 pT2 and 33pT3a). Pre-operative details (age, PSA, dig-ital rectal examination, Gleason score onbiopsies, percentage of positive biopsies)and pathological data (Gleason score,pTNM staging, DNA ploidy, ET-1 semi-quantitative immunostaining, Ki-67 prolif-
eration marker) were retrospectively com-pared between biopsies and RP specimenby the same pathologist.Results: Pre-operative PSA level washigher in pT3a group. No significant dif-ference was noted between the 2 groupsregarding percentage of positive biopsies,DNA ploidy, Ki-67 proliferation marker.Gleason score on biopsies � 7 was pre-dictive of pT3a prostate cancer(p�0.003). In region of adenocarcinoma,ET-1 expression was significantly higher inthe pT3a group on biopsies (p�0.001)and on RP specimen (p�0.001) in com-parison with the pT2 group. Using multi-variate analysis, ET-1 expression on biop-sies was an independent risk factor ofpT3a cancer with specificity�79%, sensi-tivity�69%, positive predictive value�77%and negative predictive value�72%.Conclusions: Our data suggest ET-1 is anindependent prognostic factor of pT3a onbiopsies and RP specimen. Further pro-spective studies are required to seewhether ET-1 expression on prostate bi-opsies could better select patients for clin-ically localised prostate cancer treatmentsand for adjuvant targeted therapies afterRP.
POD-5.11Predictors and Pathological Featuresof Prostate Cancer on Repeat Biopsywith High-grade ProstaticIntraepithelial Neoplasia (HPIN) and/or Atypical Small Acinar Proliferation(ASAP)Chin J1,2, Lim D1,2, Abdelhady M1,2,Downey D1,2, Izawa J1,2
1University of Western Ontario, London,Canada; 2London Health Sciences Centre,London, Canada
Introduction and Objectives: The clini-cal significance of HPIN and/or ASAPbased on transrectal ultrasound guidedbiopsy (TRUS Bx) remains controversial.We reviewed the predictors for detectionof and pathological features associatedwith prostate cancer (CaP) on repeat bi-opsy and the subsequent CaP detectionrate for patients with prior diagnosis ofHPIN, ASAP, HPIN � ASAP and no HPINor ASAP.Materials and Methods: Six hundredand ten men (mean age 61 yrs, range 48-67) underwent repeat TRUS-guided 10core Bx from 1/2003 to 12/2004. Group 1(serving as Control) consisted of 343 menwho underwent repeat TRUS Bx for risingprostate specific antigen (PSA) levelsand/or abnormal digital rectal examination(DRE) but no previous HPIN or ASAP);128 had previous HPIN only (Group 2);
89 men with previous ASAP only (Group3), and 50 men had HPIN � ASAP in pre-vious Bx (Group 4). Univariate and multi-variate logistic regression analyses wereused for analysis of clinical factors includ-ing age, family history, DRE findings, pros-tate volume, PSA, PSA density (PSAD) andTRUS findings, for the ability to predictdetection of CaP on repeat Bx. In menwith positive repeat Bx, Gleason score (ofBx and where available, radical prostatec-tomy, specimens) was correlated withpresence of previous HPIN and ASAP.Results: CaP detection rate on repeat bxwas highest for Group 3 (prior ASAP,42.7%); 29.5% for Group 1, 14.8% forGroup 2, and 30.0% for Group 4. On mul-tivariate analysis, only PSAD was found tobe an independent predictive factor forCaP with previous HPIN only. The Glea-son scores (� or �7) of those with posi-tive Bx are listed in Table 1. Out of 72men, 31 underwent radical prostatectomy.On final pathology, 3 out of the 22 pa-tients with Gleason �7 on TRUS biopsywere upgraded to 7, 5 out of 9 patientswith Gleason �7 were downgraded to 6,and 1 was upgraded from Gleason 7 to8.Thus 77.4% (24/31) had a final Gleasonscore�7.Conclusions: Patients with ASAP appearto have a higher risk of CaP detection onrepeat biopsy. No single clinical factorwas predictive of CaP on repeat Bx forpts with previous HPIN and/or ASAP ex-cept for PSAD in pts with previous HPIN.When CaP is diagnosed on repeat Bx fol-lowing prior HPIN and ASAP, the CaPwere more likely to have Gleason score�7. Vigilant follow-up with earlier repeatbiopsies especially for patients with previ-ous ASAP would be warranted for earlierdetection of CaP.
POD-5.12Pathological Disease Progression onRepeat Transrectal Biopsy in aContemporary Active SurveillanceCohort of Prostate Cancer Patients:
Table 1, POD-5.11 Gleason Score Outcomein Positive Patients with Previous HPIN and/orASAP.
Positive RepeatBiopsy (n � 72)
Gleason Score(%)
-- �7 �7Previous HPIN
(n � 19)15 (79) 4 (21)
Previous ASAP(n � 38)
27 (71) 11 (29)
Previous HPIN � ASAP(n � 15)
11 (73) 4 (27)
PODIUM SESSIONS
S48 UROLOGY 72 (Supplement 5A), November 2008