1
release of cytochrome-c to the cytosol in PC3 and stroma cells. This was inhibited in PNT1 cells. ODC activity was inhibited in PC3 cells. P 0.003 There was an in- creased ODC activity in both PNT1 and stroma P 0.002 and 0.0016 respec- tively. MTS results are reduced for PC3 but increased for PNT1 and stroma mirror- ing the ODC results. P 0.049, 0.011 and 0.008 respectively. Conclusion: Thee results indicate that NO-NSAIDs induce apoptosis in malignant epithelium and stroma but inhibit it in benign epithelium. The induction is sec- ondary to inhibition of ODC in PC3 but not in stroma. Apoptosis in stroma is sec- ondary to another pathway. The reduced apoptosis in PNT1 cells suggests a protec- tive effect on benign cells. These results suggest that NO-NSAIDs could be used to treat prostate cancer cells selectively offer- ing protection to healthy tissues. MP-08.24 Expression of the urokinase- plasminogen-activator receptor (UPA- R) in disseminated tumor cells in bone marrow and peripheral blood specimens of patients with prostate cancer Thomas C, Melchior S, Pfitzenmaier J, Gillitzer R, Thuroff J Dept. of Urology; Johannes Gutenberg University Medical Center, Mainz, Ger- many Introduction and Objective: The uroki- nase-plasminogen-activator (UPA) plays an important role in the degradation of extra- cellular matrix, thus allowing dissemi- nated circulating tumor cells to progress to manifest metastatic lesions. Previous studies have shown that the expression of UPA-R in circulating tumor cells in the bone marrow (BM) and peripheral blood (PB) of breast and colon cancer patients is associated with a poorer prognosis. Pur- pose of this study was to evaluate the ex- pression of UPA-R in BM and PB samples of prostate cancer patients prior to radical prostatectomy. Material and Methods: BM and PB sam- ples of 36 prostate cancer patients were obtained prior to radical prostatectomy. Disseminated epithelial cells were charac- terised by cytokeratin (CK) 45 and UPA-R immuno-double-staining. The results were correlated with the pathologic tumor stage and Gleason-Score. Results: In 21 of 36 (58%) patients dis- seminated epithelial cells were detected in the bone marrow by cytokeratin-immu- nocytochemistry of whom all patients also showed expression of the UPA-R. 15 of these 21 patients (72 %) had Gleason scores 7 and/or pathologic T stage of pT3. All patients with positive lymph nodes (n3) were also CK and UPA-R positive in the bone marrow. In 6 of 36 (16%) patients, all with Gleason Scores of 8, disseminated epithelial cells were de- tected in the PB. Conclusions: In approximately 58% of prostate cancer patients, CK/UPA-R posi- tive cells can be detected in the bone marrow prior to radical prostatectomy. Patients with adverse histopathological features were more likely to have detect- able CK/UPA-R cells. Detection rates in the peripheral blood were considerably lower than in the bone marrow. Detec- tion of the UPA-R is a promising method for further characterisation of circulating tumor cells. MP-08.25 Gleason score migration between prostate biopsy and prostatectomy specimens in a contemporary series of patients undergoing radical prostatectomy Thomas C, Gillitzer R, Thuroff J, Melchior S Department of Urology; Johannes Guten- berg University Medical School, Mainz, Germany Introduction: The Gleason score as- signed on prostate biopsy specimens is frequently used in preoperative nomo- grams to counsel prostate cancer patients prior to definitive therapy. It should re- flect the final score of the radical prosta- tectomy specimens. In this study we eval- uated the rate of overgrading and undergrading in prostate biopsy speci- mens in a contemporary series of patients undergoing radical prostatectomy. Material and Methods: Between Octo- ber 2002 and December 2004, 645 pa- tients underwent radical prostatectomy for clinically localized prostate cancer. All patients had undergone 12 core ultra- sound guided prostate biopsies prior to surgery. Patients were grouped according to their Gleason scores as low grade (Gleason score 2-6), intermediate (Gleason score 7) and high grade (Gleason score 8-10). Results: Overall, 394/645 patients (61 %) were accurately scored when comparing biopsy and prostatectomy specimens. 161 patients (25 %) were undergraded and 90 (14 %) were overgraded, respectively. Among patients in the low risk group, 35 % were undergraded in the prostate bi- opsy specimen resulting in a worse prog- nostic classification after radical prostatec- tomy. Vice versa, in the high risk group 51 % of patients had been overgraded re- sulting in a better prognostic classification following surgery. Conclusions: In this contemporary series of patients undergoing radical prostatec- tomy undergrading and overgrading was a frequent phenomenon when comparing biopsy and prostatectomy specimens. These results have important implications when using nomograms for counselling patients prior to definitive therapy. MP-08.26 Genetic polymorphisms of genes involved in androgen metabolism and synthesis pathway and prostate cancer risk among Chinese population Li M, Guan T, Na Y Department of Urology, First Hospital, Institute of Urology, Peking University, Beijing, China Introduction: Ethnic and geographic dif- ferences in prostate cancer incidence have been well documented, in which the genetic polymorphisms were hypothe- sized to be the possible reason for the racial differences. We conducted a case- control study to evaluate the association between polymorphisms in genes in- volved in the androgen biosynthesis and metabolism pathway and the risk of pros- tate cancer among Chinese population. Methods: One hundred sixteen patients with the pathologic diagnosis of prostate cancer and 190 healthy age-matched male controls were enrolled in this study. All DNA samples from peripheral blood were genotyped by RFLP and DHPLC for poly- morphisms in genes including androgen receptor (AR), vitamin D receptor (VDR), 5-alpha-reductase type II (SRD5A2) and p450c17 (CYP17) genes. The different polymorphisms in prostate cancer patients were also analyzed according to age of onset, prostate-specific antigen level, can- cer stage and grade (Gleason score). Results: Statistical analysis of AR geno- type prevalence showed significant differ- ence between prostate cancer patients and controls (p0.05). The Odds Ratio (OR) for prostate cancer was 2.39 (95%CI 1.19-4.81, P0.012) when individuals with short CAG repeats (22) were com- pared with those having long repeats (22). CAG repeat length was also signifi- cantly associated with cancer stage (T3/T4 vs T1/T2) and grade (P0.05), but no as- sociated with age of onset and prostate- specific antigen (PSA) level at diagnosis. No significant differences of the frequen- cies of VDR, SRD5A2 and CYP17 geno- MODERATED POSTER SESSIONS 104 UROLOGY 68 (Supplement 5A), November 2006

MP-08.25: Gleason score migration between prostate biopsy and prostatectomy specimens in a contemporary series of patients undergoing radical prostatectomy

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release of cytochrome-c to the cytosol inPC3 and stroma cells. This was inhibitedin PNT1 cells. ODC activity was inhibitedin PC3 cells. P � 0.003 There was an in-creased ODC activity in both PNT1 andstroma P � 0.002 and 0.0016 respec-tively. MTS results are reduced for PC3but increased for PNT1 and stroma mirror-ing the ODC results. P � 0.049, 0.011 and0.008 respectively.Conclusion: Thee results indicate thatNO-NSAIDs induce apoptosis in malignantepithelium and stroma but inhibit it inbenign epithelium. The induction is sec-ondary to inhibition of ODC in PC3 butnot in stroma. Apoptosis in stroma is sec-ondary to another pathway. The reducedapoptosis in PNT1 cells suggests a protec-tive effect on benign cells. These resultssuggest that NO-NSAIDs could be used totreat prostate cancer cells selectively offer-ing protection to healthy tissues.

MP-08.24Expression of the urokinase-plasminogen-activator receptor (UPA-R) in disseminated tumor cells inbone marrow and peripheral bloodspecimens of patients with prostatecancerThomas C, Melchior S, Pfitzenmaier J,Gillitzer R, Thuroff JDept. of Urology; Johannes GutenbergUniversity Medical Center, Mainz, Ger-many

Introduction and Objective: The uroki-nase-plasminogen-activator (UPA) plays animportant role in the degradation of extra-cellular matrix, thus allowing dissemi-nated circulating tumor cells to progressto manifest metastatic lesions. Previousstudies have shown that the expression ofUPA-R in circulating tumor cells in thebone marrow (BM) and peripheral blood(PB) of breast and colon cancer patients isassociated with a poorer prognosis. Pur-pose of this study was to evaluate the ex-pression of UPA-R in BM and PB samplesof prostate cancer patients prior to radicalprostatectomy.Material and Methods: BM and PB sam-ples of 36 prostate cancer patients wereobtained prior to radical prostatectomy.Disseminated epithelial cells were charac-terised by cytokeratin (CK) 45 and UPA-Rimmuno-double-staining. The results werecorrelated with the pathologic tumorstage and Gleason-Score.Results: In 21 of 36 (58%) patients dis-seminated epithelial cells were detectedin the bone marrow by cytokeratin-immu-nocytochemistry of whom all patients alsoshowed expression of the UPA-R. 15 of

these 21 patients (72 %) had Gleasonscores � 7 and/or pathologic T stage ofpT3. All patients with positive lymphnodes (n�3) were also CK and UPA-Rpositive in the bone marrow. In 6 of 36(16%) patients, all with Gleason Scores of8, disseminated epithelial cells were de-tected in the PB.Conclusions: In approximately 58% ofprostate cancer patients, CK/UPA-R posi-tive cells can be detected in the bonemarrow prior to radical prostatectomy.Patients with adverse histopathologicalfeatures were more likely to have detect-able CK/UPA-R cells. Detection rates inthe peripheral blood were considerablylower than in the bone marrow. Detec-tion of the UPA-R is a promising methodfor further characterisation of circulatingtumor cells.

MP-08.25Gleason score migration betweenprostate biopsy and prostatectomyspecimens in a contemporary seriesof patients undergoing radicalprostatectomyThomas C, Gillitzer R, Thuroff J,Melchior SDepartment of Urology; Johannes Guten-berg University Medical School, Mainz,Germany

Introduction: The Gleason score as-signed on prostate biopsy specimens isfrequently used in preoperative nomo-grams to counsel prostate cancer patientsprior to definitive therapy. It should re-flect the final score of the radical prosta-tectomy specimens. In this study we eval-uated the rate of overgrading andundergrading in prostate biopsy speci-mens in a contemporary series of patientsundergoing radical prostatectomy.Material and Methods: Between Octo-ber 2002 and December 2004, 645 pa-tients underwent radical prostatectomyfor clinically localized prostate cancer. Allpatients had undergone 12 core ultra-sound guided prostate biopsies prior tosurgery. Patients were grouped accordingto their Gleason scores as low grade(Gleason score 2-6), intermediate (Gleasonscore 7) and high grade (Gleason score8-10).Results: Overall, 394/645 patients (61 %)were accurately scored when comparingbiopsy and prostatectomy specimens. 161patients (25 %) were undergraded and 90(14 %) were overgraded, respectively.Among patients in the low risk group, 35% were undergraded in the prostate bi-opsy specimen resulting in a worse prog-nostic classification after radical prostatec-

tomy. Vice versa, in the high risk group51 % of patients had been overgraded re-sulting in a better prognostic classificationfollowing surgery.Conclusions: In this contemporary seriesof patients undergoing radical prostatec-tomy undergrading and overgrading was afrequent phenomenon when comparingbiopsy and prostatectomy specimens.These results have important implicationswhen using nomograms for counsellingpatients prior to definitive therapy.

MP-08.26Genetic polymorphisms of genesinvolved in androgen metabolism andsynthesis pathway and prostatecancer risk among ChinesepopulationLi M, Guan T, Na YDepartment of Urology, First Hospital,Institute of Urology, Peking University,Beijing, China

Introduction: Ethnic and geographic dif-ferences in prostate cancer incidencehave been well documented, in which thegenetic polymorphisms were hypothe-sized to be the possible reason for theracial differences. We conducted a case-control study to evaluate the associationbetween polymorphisms in genes in-volved in the androgen biosynthesis andmetabolism pathway and the risk of pros-tate cancer among Chinese population.Methods: One hundred sixteen patientswith the pathologic diagnosis of prostatecancer and 190 healthy age-matched malecontrols were enrolled in this study. AllDNA samples from peripheral blood weregenotyped by RFLP and DHPLC for poly-morphisms in genes including androgenreceptor (AR), vitamin D receptor (VDR),5-alpha-reductase type II (SRD5A2) andp450c17 (CYP17) genes. The differentpolymorphisms in prostate cancer patientswere also analyzed according to age ofonset, prostate-specific antigen level, can-cer stage and grade (Gleason score).Results: Statistical analysis of AR geno-type prevalence showed significant differ-ence between prostate cancer patientsand controls (p�0.05). The Odds Ratio(OR) for prostate cancer was 2.39 (95%CI1.19-4.81, P�0.012) when individualswith short CAG repeats (�22) were com-pared with those having long repeats(�22). CAG repeat length was also signifi-cantly associated with cancer stage (T3/T4vs T1/T2) and grade (P�0.05), but no as-sociated with age of onset and prostate-specific antigen (PSA) level at diagnosis.No significant differences of the frequen-cies of VDR, SRD5A2 and CYP17 geno-

MODERATED POSTER SESSIONS

104 UROLOGY 68 (Supplement 5A), November 2006