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C33 BPH AND INFLAMMATION - IS THERE A RELATION?
Introduction & Objectives: The most studied epigenetic modification in prostate cancer (CaP) is the methylation of promoter regions of different genes. Currently, the best-characterized gene that is methylated in CaP is glutathione S-transferase-π (GSTP1). The frequency of methylation of genes such as E-cad and PTGS2 was also higher in prostate carcinoma compared with BPH. Material & Methods: We optimized a nested MSP method and investigated the methylation status of a panel of genes (GSTP1, PTGS2, E-cad) in 85 prostate cancer patients, 83 pathological reviewed surrounding non-neoplastic tissue (SNNT) adjacent to the matched CaP and 20 benign prostate hyperplasia (BPH) samples. Results: The positive methylation status was detected in 98,8% (84/85) for GSTP1, 41,2% (35/85) for E-cadherin, and 88,2% (75/85) for PTGS2 gene in cancer tissue and in 36,1% (30/83), 25,3% (21/83), and 41% (34/83) in pathological reviewed surrounding non-neoplastic tissue (SNNT) adjacent to the matched CaP, respectively. No methylation activity was observed for prostatic tissues exhibiting simple benign hyperplasia. The multiple variable analyses revealed a decreased trend in methylation positivity of all analyzed genes from CaP, through SNNT to BPH (p<0.0001) and this difference was maintained not only for cancer tissue compared to SNNT or BPH, but also for methylation positivity between SNNT and BPH (for GSTP1 and PTGS2 p<0.01; for Ecad p<0.05). Conclusions: Our results suggest that hypermethylation of genes GSTP1, PTGS2, E-cad can not only safely distinguish prostate cancinomas from benign prostate tissues, but may warrant surgeons from the presence of invasive cancer when SNNT with methylation positivity is reported in pathological findings from prostatic biopsies/missbiopsies.
C31
Association of inflammation and IL-6 polymorphism with prostate hyperplasia and prostate cancer
Simunovic D.1, Cosic I.1, Sudarevic B.1, Mandic S.2, Horvat H.2, Marczi S.3, Pavlovic O.1, Rakin I.1, Perkovic J.1, Radoja I.1, Galic J.1 1 University Hospital Osijek, Dept. of Urology, Osijek, Croatia, 2University Hospital Osijek, Dept. of Biochemistry, Osijek, Croatia, 3University Hospital Osijek, Dept. of Molecular Diagnostic and Tissue Typing, Osijek, Croatia Introduction & Objectives: Prostate cancer (PC) is most common cancer in men and benign prostate hyperplasia (BPH) is condition affecting majority of elder men with great impact on everyday life. Both genetic and environmental factors are involved in development of PC. Epidemiological studies have shown that inflammation, toxins, hormonal changes or trauma are risk factors of PC, suggesting that chronic inflammation can lead to PC. IL-6 is a cytokine expressed in inflammation processes. Polymorphisms in gene for IL-6 are responsible for different production of IL-6. Aim of our prospective study was to analyze correlation of inflammation and IL-6 high producer (GG or GC genotype) with presentation and symptoms of PC and BPH. Material & Methods: We started selecting patients in March of 2008 and 120 PC and 120 BPH patients, age matched groups, were included after giving informed consent. In all patients history was taken and urological exam was done before prostate biopsy was performed (only patients undergoing biopsy were included). Genomic DNA was extracted from whole blood and genotype polymorphism for IL-6 was assessed by real-time PCR. Results: PC in family history was more common in PC group (8,3% vs. 5.8%, p=0.169), prostate were larger in BPH group (76 ccm vs. 51 ccm, p=0.0001) and inflammation on histology was more common in BPH group (91.3% vs. 49.1%, p=0.001). There was no difference in mean IPSS score between groups (14 vs. 13, p=0.488). High producer genotype (GG or GC) of IL-6 was present in 86.7% of BPH patients and 80.8% of PC patients (p=0.147) and there was uniform distribution of high producers between PC groups (by differentiation, p=0.601). Odds ratio for BPH patient to be high IL-6 producer was 1.54, with 95% CI 0.77-3.09. There was no difference in high producer genotype in patients with or without inflammation on histology in both groups (p=0.209 and p=0.300), but high producers are more common in BPH then in PC patients with inflammation (87,3% vs. 77.6%, p=0.09). High producer genotype is evenly distributed when prostate size was accounted (volume <40, 41-80, >81 ccm) in BPH group, but more high producers are noted in larger prostates of PC patients (73%, 79%, 85%). However, this difference is not significant when prostate of same size are compared between groups. Conclusions: We found no difference in IL-6 producers between PC and BPH patients in our population. Inflammation is more common in BPH and ratio of IL-6 high producers is much higher in BPH patients with inflammation, suggesting limited role in PC. Higher ratio of high producers in patients with larger prostate can be explained with higher growth promotion by mediators of inflammation. Although some studies have not found a positive role of high producer IL-6 in PC development, contradictory results of published results have lead to proposed explanation of ethnic differences in IL-6 producers and effect on population.
C32
Men with benign prostate hyperplasia have higher plasma antibody levels aganist cytomegalovirus and human papillomavirus 18 than prostate cancer patients
Hrbacek J.1, Hamsikova E.2, Tachezy R.2, Eis V.3, Brabec M.4, Urban M.5, Heracek J.5 1 Charles University In Prague, 3rd Faculty of Medicine, Hospital of Kralovske Vinohrady, Dept. of Urology, Prague, Czech Republic, 2Institute of Hematology and Blood Transfusion, Prague, Czech Republic, 3Charles University In Prague, 3rd Faculty of Medicine, Hospital of Kralovske Vinohrady, Dept. of Pathology, Prague, Czech Republic, 4National Health Institute, Prague, Czech Republic, 5 Charles University In Prague, 3rd Faculty of Medicine, Hospital of Kralovske Vinohrady; Androgeos, Dept. of Urology, Prague, Czech Republic Introduction & Objectives: Many human malignancies are associated with infection. The aim of the study was to compare plasma antibody levels against common genitourinary pathogens in prostate cancer (PC) patients and benign prostate hyperplasia (BPH) patients. Material & Methods: The study population consisted of 330 men after radical retropubic prostatectomy with a histopathological finding of localized or locally advanced prostate cancer and 106 control subjects who underwent open simple prostatectomy with no malignant structures in the surgery specimen. In the PC group, the average age was 64 years (39-81), mean prostate specific antigen (PSA) level 9.01 ng/mL (0.81-35.40), median Gleason score 6 (3-9); there were 50.9% of localized cancers ≤pT2c and 49.1% of locally advanced cancers ≥pT3a. In the BPH group, the average age was 72 years (54-87) and mean PSA level 7.50 ng/mL (0.89-39.00). We investigated the presence of antibodies against human cytomegalovirus (CMV), herpes simplex virus type 1 and 2, human papillomaviruses (HPV) 6, 11, 16, 18, 31 and 33, Chlamydia trachomatis and Treponema pallidum using ELISA (enzyme-linked immunosorbent assay). Complement fixation test was used to assess antibodies against Neisseria gonorrhoeae. Mean plasma antibody levels were compared using two sample Wilcoxon test. Results: The only statistically significant difference was found in case of CMV (p=0.0003) and HPV 18 (p=0.0035). Higher plasma antibody levels were detected in BPH patients compared with the PC group (3.870 vs. 3.154 for CMV; 0.706 vs. 0.617 for HPV 18). Other differences were not statistically significant. Conclusions: The serology results do not support the idea of PC being associated with infection by any of the pathogens studied. On the contrary, an inverse correlation was noted for CMV and HPV 18. Similar results are occasionally found in the literature for different pathogens. Whether infection plays a protective role and in what manner, is not known and can be investigated further. The study was funded by the Internal Grant Agency of the Ministry of Health, grant no. NS9984.
C33
BPH and inflammation – is there a relation?
Alexandrescu A.E., Multescu M.R., Geavlete G.E., Geavlete G.P. Saint John Clinical Emergency Hospital, Dept. of Urology, Bucharest, Romania Introduction & Objectives: Recent studies demonstrated the association between BPH and intraprostatic inflammatory changes. This study aimed to identify their incidence as well as the way they influence the preoperative characteristics of the patients. Material & Methods: Postoperative hystopathological exams of 1000 patients with BPH (retropubic prostatectomy and TURP specimens) were retrospectively reviewed. Preoperative IPSS score, prostate volume, maximal urinary flow (Qmax) and total PSA levels were also evaluated. Results: Inflammatory changes were identified in 52% of the reviewed specimens, most of them with chronic lesions (86.9%). These patients had statistically significant larger mean prostate volume (72 g vs. 56 g), increased IPSS (19 vs. 12) and higher PSA levels (3.49 ng/ml vs. 1.88 ng/ml). Regarding the Qmax, the differences between patients with or without inflammatory lesions were not significant: 14.3 ml/sec vs. 14.1 ml/sec. Postoperative urinary retention rate was 7.2% in patients with prostate inflammation and only 3.8% in those without these types of lesions. Conclusions: Inflammatory lesions occur in over half of the patients who underwent surgery for BPH. Their presence seems to influence not only the preoperative characteristics but also the postoperative evolution. However, supplementary studies are necessary to evaluate the impact of these changes over the BPH diagnosis and treatment.
Eur Urol Suppl 2010;9(6):627
C31
Association of inflammation and IL-6 polymorphism with prostate hyperplasia and prostate cancer
Simunovic D.1, Cosic I.1, Sudarevic B.1, Mandic S.2, Horvat H.2, Marczi S.3, Pavlovic O.1, Rakin I.1, Perkovic J.1, Radoja I.1, Galic J.1 1 University Hospital Osijek, Dept. of Urology, Osijek, Croatia, 2University Hospital Osijek, Dept. of Biochemistry, Osijek, Croatia, 3University Hospital Osijek, Dept. of Molecular Diagnostic and Tissue Typing, Osijek, Croatia Introduction & Objectives: Prostate cancer (PC) is most common cancer in men and benign prostate hyperplasia (BPH) is condition affecting majority of elder men with great impact on everyday life. Both genetic and environmental factors are involved in development of PC. Epidemiological studies have shown that inflammation, toxins, hormonal changes or trauma are risk factors of PC, suggesting that chronic inflammation can lead to PC. IL-6 is a cytokine expressed in inflammation processes. Polymorphisms in gene for IL-6 are responsible for different production of IL-6. Aim of our prospective study was to analyze correlation of inflammation and IL-6 high producer (GG or GC genotype) with presentation and symptoms of PC and BPH. Material & Methods: We started selecting patients in March of 2008 and 120 PC and 120 BPH patients, age matched groups, were included after giving informed consent. In all patients history was taken and urological exam was done before prostate biopsy was performed (only patients undergoing biopsy were included). Genomic DNA was extracted from whole blood and genotype polymorphism for IL-6 was assessed by real-time PCR. Results: PC in family history was more common in PC group (8,3% vs. 5.8%, p=0.169), prostate were larger in BPH group (76 ccm vs. 51 ccm, p=0.0001) and inflammation on histology was more common in BPH group (91.3% vs. 49.1%, p=0.001). There was no difference in mean IPSS score between groups (14 vs. 13, p=0.488). High producer genotype (GG or GC) of IL-6 was present in 86.7% of BPH patients and 80.8% of PC patients (p=0.147) and there was uniform distribution of high producers between PC groups (by differentiation, p=0.601). Odds ratio for BPH patient to be high IL-6 producer was 1.54, with 95% CI 0.77-3.09. There was no difference in high producer genotype in patients with or without inflammation on histology in both groups (p=0.209 and p=0.300), but high producers are more common in BPH then in PC patients with inflammation (87,3% vs. 77.6%, p=0.09). High producer genotype is evenly distributed when prostate size was accounted (volume <40, 41-80, >81 ccm) in BPH group, but more high producers are noted in larger prostates of PC patients (73%, 79%, 85%). However, this difference is not significant when prostate of same size are compared between groups. Conclusions: We found no difference in IL-6 producers between PC and BPH patients in our population. Inflammation is more common in BPH and ratio of IL-6 high producers is much higher in BPH patients with inflammation, suggesting limited role in PC. Higher ratio of high producers in patients with larger prostate can be explained with higher growth promotion by mediators of inflammation. Although some studies have not found a positive role of high producer IL-6 in PC development, contradictory results of published results have lead to proposed explanation of ethnic differences in IL-6 producers and effect on population.
C32
Men with benign prostate hyperplasia have higher plasma antibody levels aganist cytomegalovirus and human papillomavirus 18 than prostate cancer patients
Hrbacek J.1, Hamsikova E.2, Tachezy R.2, Eis V.3, Brabec M.4, Urban M.5, Heracek J.5 1 Charles University In Prague, 3rd Faculty of Medicine, Hospital of Kralovske Vinohrady, Dept. of Urology, Prague, Czech Republic, 2Institute of Hematology and Blood Transfusion, Prague, Czech Republic, 3Charles University In Prague, 3rd Faculty of Medicine, Hospital of Kralovske Vinohrady, Dept. of Pathology, Prague, Czech Republic, 4National Health Institute, Prague, Czech Republic, 5 Charles University In Prague, 3rd Faculty of Medicine, Hospital of Kralovske Vinohrady; Androgeos, Dept. of Urology, Prague, Czech Republic Introduction & Objectives: Many human malignancies are associated with infection. The aim of the study was to compare plasma antibody levels against common genitourinary pathogens in prostate cancer (PC) patients and benign prostate hyperplasia (BPH) patients. Material & Methods: The study population consisted of 330 men after radical retropubic prostatectomy with a histopathological finding of localized or locally advanced prostate cancer and 106 control subjects who underwent open simple prostatectomy with no malignant structures in the surgery specimen. In the PC group, the average age was 64 years (39-81), mean prostate specific antigen (PSA) level 9.01 ng/mL (0.81-35.40), median Gleason score 6 (3-9); there were 50.9% of localized cancers ≤pT2c and 49.1% of locally advanced cancers ≥pT3a. In the BPH group, the average age was 72 years (54-87) and mean PSA level 7.50 ng/mL (0.89-39.00). We investigated the presence of antibodies against human cytomegalovirus (CMV), herpes simplex virus type 1 and 2, human papillomaviruses (HPV) 6, 11, 16, 18, 31 and 33, Chlamydia trachomatis and Treponema pallidum using ELISA (enzyme-linked immunosorbent assay). Complement fixation test was used to assess antibodies against Neisseria gonorrhoeae. Mean plasma antibody levels were compared using two sample Wilcoxon test. Results: The only statistically significant difference was found in case of CMV (p=0.0003) and HPV 18 (p=0.0035). Higher plasma antibody levels were detected in BPH patients compared with the PC group (3.870 vs. 3.154 for CMV; 0.706 vs. 0.617 for HPV 18). Other differences were not statistically significant. Conclusions: The serology results do not support the idea of PC being associated with infection by any of the pathogens studied. On the contrary, an inverse correlation was noted for CMV and HPV 18. Similar results are occasionally found in the literature for different pathogens. Whether infection plays a protective role and in what manner, is not known and can be investigated further. The study was funded by the Internal Grant Agency of the Ministry of Health, grant no. NS9984.
C33
BPH and inflammation – is there a relation?
Alexandrescu A.E., Multescu M.R., Geavlete G.E., Geavlete G.P. Saint John Clinical Emergency Hospital, Dept. of Urology, Bucharest, Romania Introduction & Objectives: Recent studies demonstrated the association between BPH and intraprostatic inflammatory changes. This study aimed to identify their incidence as well as the way they influence the preoperative characteristics of the patients. Material & Methods: Postoperative hystopathological exams of 1000 patients with BPH (retropubic prostatectomy and TURP specimens) were retrospectively reviewed. Preoperative IPSS score, prostate volume, maximal urinary flow (Qmax) and total PSA levels were also evaluated. Results: Inflammatory changes were identified in 52% of the reviewed specimens, most of them with chronic lesions (86.9%). These patients had statistically significant larger mean prostate volume (72 g vs. 56 g), increased IPSS (19 vs. 12) and higher PSA levels (3.49 ng/ml vs. 1.88 ng/ml). Regarding the Qmax, the differences between patients with or without inflammatory lesions were not significant: 14.3 ml/sec vs. 14.1 ml/sec. Postoperative urinary retention rate was 7.2% in patients with prostate inflammation and only 3.8% in those without these types of lesions. Conclusions: Inflammatory lesions occur in over half of the patients who underwent surgery for BPH. Their presence seems to influence not only the preoperative characteristics but also the postoperative evolution. However, supplementary studies are necessary to evaluate the impact of these changes over the BPH diagnosis and treatment.
Eur Urol Suppl 2010;9(6):627