Transcript

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

Recommended