1
transcribed into cDNA. Primers and Taq- Man probes for the cDNA-specific real- time quantitative PCR assay were designed for the four molecular markers under study and GAPDH. The level of GAPDH expression was measured in all samples to normalize for sample-to-sample differences in 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%) and prostate 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 the mean /- SD of the relative expression for patients with prostate cancer compared to those with BPH and prostatitis was signifi- cantly higher for AMACR (p 0.002), EZH2 (p0.03); significantly lower for Her2/neu (p0.01) and not significantly different for survivin (p0.55). Patients with high grade prostate intraepithelial neoplasia (PIN) had higher AMACR (p0.001) and EZH2 (p 0.001) expres- sion ratios compared with survivin (NS) and Her2/neu (NS). Conclusions: These data demonstrate that AMACR, EZH2 and Her2/neu expres- sion in primary lesions of the prostate are not affected by the presence of varying grades of inflammation of the prostate and can therefore be important predictive markers of prostate cancer aggressiveness. POD-5.10 Endothelin-1 Immunostaining as a Prognostic Marker of pT3a Adenocarcinoma on Prostate Biopsies Menard J 1 , Perez T 1 , Joseph K 2 , Birembaut P 2 , Staerman F 1 1 Department of Urology and Andrology, CHU Reims, Reims, France; 2 Department of Pathology, CHU Reims, Reims, France Introduction and Objectives: To evalu- ate immunohistochemical expression of endothelin-1 (ET-1) as a prognostic marker of pT3a prostate cancer on prostate biop- sies. We compared pathological data and ET-1 immunostaining on biopsies and prostate surgical specimen between pT2 and pT3a tumors. Material and Methods: Sixty-eight radi- cal prostatectomies (RP) were realized for clinically localised prostate cancer diag- nosed on needle biopsies (35 pT2 and 33 pT3a). Pre-operative details (age, PSA, dig- ital rectal examination, Gleason score on biopsies, 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 specimen by the same pathologist. Results: Pre-operative PSA level was higher in pT3a group. No significant dif- ference was noted between the 2 groups regarding percentage of positive biopsies, DNA ploidy, Ki-67 proliferation marker. Gleason score on biopsies 7 was pre- dictive of pT3a prostate cancer (p0.003). In region of adenocarcinoma, ET-1 expression was significantly higher in the pT3a group on biopsies (p0.001) and on RP specimen (p0.001) in com- parison with the pT2 group. Using multi- variate analysis, ET-1 expression on biop- sies was an independent risk factor of pT3a cancer with specificity79%, sensi- tivity69%, positive predictive value77% and negative predictive value72%. Conclusions: Our data suggest ET-1 is an independent prognostic factor of pT3a on biopsies and RP specimen. Further pro- spective studies are required to see whether ET-1 expression on prostate bi- opsies could better select patients for clin- ically localised prostate cancer treatments and for adjuvant targeted therapies after RP. POD-5.11 Predictors and Pathological Features of Prostate Cancer on Repeat Biopsy with High-grade Prostatic Intraepithelial Neoplasia (HPIN) and/ or Atypical Small Acinar Proliferation (ASAP) Chin J 1,2 , Lim D 1,2 , Abdelhady M 1,2 , Downey D 1,2 , Izawa J 1,2 1University of Western Ontario, London, Canada; 2 London Health Sciences Centre, London, Canada Introduction and Objectives: The clini- cal significance of HPIN and/or ASAP based on transrectal ultrasound guided biopsy (TRUS Bx) remains controversial. We reviewed the predictors for detection of and pathological features associated with prostate cancer (CaP) on repeat bi- opsy and the subsequent CaP detection rate for patients with prior diagnosis of HPIN, ASAP, HPIN ASAP and no HPIN or ASAP. Materials and Methods: Six hundred and ten men (mean age 61 yrs, range 48- 67) underwent repeat TRUS-guided 10 core Bx from 1/2003 to 12/2004. Group 1 (serving as Control) consisted of 343 men who underwent repeat TRUS Bx for rising prostate specific antigen (PSA) levels and/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 (Group 3), and 50 men had HPIN ASAP in pre- vious Bx (Group 4). Univariate and multi- variate logistic regression analyses were used for analysis of clinical factors includ- ing age, family history, DRE findings, pros- tate volume, PSA, PSA density (PSAD) and TRUS findings, for the ability to predict detection of CaP on repeat Bx. In men with positive repeat Bx, Gleason score (of Bx and where available, radical prostatec- tomy, specimens) was correlated with presence of previous HPIN and ASAP. Results: CaP detection rate on repeat bx was highest for Group 3 (prior ASAP, 42.7%); 29.5% for Group 1, 14.8% for Group 2, and 30.0% for Group 4. On mul- tivariate analysis, only PSAD was found to be an independent predictive factor for CaP with previous HPIN only. The Glea- son scores ( or 7) of those with posi- tive Bx are listed in Table 1. Out of 72 men, 31 underwent radical prostatectomy. On final pathology, 3 out of the 22 pa- tients with Gleason 7 on TRUS biopsy were upgraded to 7, 5 out of 9 patients with Gleason 7 were downgraded to 6, and 1 was upgraded from Gleason 7 to 8.Thus 77.4% (24/31) had a final Gleason score7. Conclusions: Patients with ASAP appear to have a higher risk of CaP detection on repeat biopsy. No single clinical factor was predictive of CaP on repeat Bx for pts 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 CaP were more likely to have Gleason score 7. Vigilant follow-up with earlier repeat biopsies especially for patients with previ- ous ASAP would be warranted for earlier detection of CaP. POD-5.12 Pathological Disease Progression on Repeat Transrectal Biopsy in a Contemporary Active Surveillance Cohort of Prostate Cancer Patients: Table 1, POD-5.11 Gleason Score Outcome in Positive Patients with Previous HPIN and/or ASAP. Positive Repeat Biopsy (n 72) Gleason Score (%) -- 7 7 Previous 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

POD-5.11: Predictors and Pathological Features of Prostate Cancer on Repeat Biopsy with High-grade Prostatic Intraepithelial Neoplasia (HPIN) and/or Atypical Small Acinar Proliferation

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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