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IS THERE A CORRELATION BETWEEN IMMUNE RESPONSE WITHIN THE TUMOUR AND PSA PROGRESSION FREE SURVIVAL FOLLOWING RRP IN PATIENTS WITH CLINICALLY LOCALISED PROSTATE CANCER?
823
824
CARBON NANOTUBES: A NANOCONTAINER MEDIATES TRANSPORT OF CHEMOTHERAPEUTICS
ANTAGONISTIC EFFECTS OF SODIUM BUTYRATE AND N-(4HYDROXYPHENYL)RETINAMIDE ON PROSTATE CANCER
Kunze D.1, Hampel S.2, Kraemer K.1, Haase D.2, Fuessel S.1, Leonhardt A.2, Meye A.1, Buechner B.2, Grimm M.O.1, Wirth M.P.1
Kuefer R.1, Genze F.1, Zugmaier W.2, Rinnab L.1, Hautmann R.E.2, Buechele B.2
Technical University of Dresden, Dept. of Urology, Dresden, Germany, 2Institute for Solid State and Materials Research, IFW, Dresden, Germany 1
Introduction & Objectives: Multiwalled carbon nanotubes (CNTs) are cylindrical structures with 40-60 nm in diameter and a few µm in length. Their hollow core is surrounded by various carbon shells. CNTs are characterized by a high aspect ration and high mechanical and FKHPLFDOVWDELOLW\7KHLUH[WUDRUGLQDU\SURSHUWLHVPDNH&17VLQWHUHVWLQJWRROVIRUDZLGHᚏHOG of applications, e.g. in material sciences, biology and medicine. The aim of the present study was the development of a nano-scaled container for drug delivery. Therefore, an approach IRU ᚏOOLQJ RI &17V E\ SODWLQXPEDVHG FKHPRWKHUDSHXWLF GUXJV ZDV GHYHORSHG DQG WKHLU F\WRWR[LFHᚎHFWVZHUHWHVWHGLQDFHOOFXOWXUHPRGHO Material & Methods: CNTs were synthesized by chemical vapouB, Dept. of ur deposition (CVD) with iron as catalyst in a solid source CVD-system. A liquid phase method using water DV VROYHQW ZDV XVHG WR ᚏOO &17V ZLWK FDUERSODWLQ RU FLVSODWLQ &7&17V +XPDQ VHUXP DOEXPLQ PHGLDWHG WKH GLVSHUVLRQ RI QDWXUDOO\ K\GURSKRELF &17V LQ SKRVSKDWH EXᚎHUHG saline. The amount of platinum that can be transported by CT-CNTs and release kinetics ZHUHTXDQWLᚏHGE\DWRPLFDEVRUSWLRQVSHFWURVFRS\7KHSURVWDWHFDQFHUFHOOOLQHV3&DQG '8 ZHUH WUHDWHG ZLWK GLᚎHUHQW FRQFHQWUDWLRQV RI HPSW\ &17V GUXJ ᚏOOHG &7&17V RU free drug, respectively. After incubation for 24h, cells were washed and incubated in fresh medium until examination of cellular viability (WST-1 assay), cell count, apoptosis (annexin V staining) and cell cycle distribution. Results: Empty CNTs did not alter the growth features of neither tumour cells nor nonPDOLJQDQWᚏEUREODVWVXQGHUWKHFRQGLWLRQVWHVWHG)XUWKHUPRUHWKHFHOOXODUXSWDNHRI&17V ZDVFRQᚏUPHG$IWHUV\QWKHVLVHPSW\&17VFRXOGEHUHRSHQHGDQGᚏOOHGZLWKFDUERSODWLQ DQG FLVSODWLQ 7KH SODWLQXP ᚏOOLQJ ZDV FOHDUO\ YLVLEOH DV EODFN GRWV LQVLGH RI &7&17V E\ PHDQVRIWUDQVPLVVLRQHOHFWURQPLFURVFRS\$ᚏOOLQJ\LHOGRIDERXW ZZ ZDVUHDFKHG CT-CNTs have been shown to release the incorporated drugs in the culture medium within K7KHHᚎHFWLYHQHVVRIWKHFKHPRWKHUDSHXWLFDIWHUUHOHDVHIURP&7&17VZDVVKRZQLQ cell culture experiments. CT-CNTs induced a concentration-dependent inhibition of viability, reduced cell numbers, induced apoptosis and caused a cell cycle arrest in G2/M. Conclusions: 7KLV SUHOLPLQDU\ VWXG\ GHVFULEHV WKH V\QWKHVLV DQG IXQFWLRQ RI &17V ᚏOOHG with chemotherapeutic drugs. These potential nanocontainers for drug delivery are nonWR[LFE\WKHPVHOYHVFDQEHᚏOOHGZLWKGUXJVDQGUHOHDVHWKHPRYHUWLPHWRSURPRWHSRWHQW DQWLSUROLIHUDWLYHHᚎHFWVRQSURVWDWHFDQFHUFHOOV
1 University of Ulm, Dept. of Urology, Ulm, Germany, 2University of Ulm, Dept. of Pharmacology and Natural Products, Ulm, Germany
Introduction & Objectives: Butyrates and retinoids are promising agents for the treatment of various tumours. In prostate cancer both drugs have demonstrated antineoplastic activity. In this study we set out to analyse a combinational WUHDWPHQW H[SHFWLQJ DQ DGGLWLYH WUHDWPHQW HᚎHFW ZLWK OHVV VLGH HᚎHFWV GXH WR reduced dosages of the single drugs. Material & Methods: 7KH HᚎHFW RI VRGLXP EXW\UDWH DQG 1 K\GUR[\SKHQ\O UHWLQDPLGH +35 RQ SURVWDWH FDQFHU FHOOV 3& DQG /1&D3 DV PRQRWKHUDS\ or in combination was tested in vitro and in vivo. For the in vitro analysis, viability and apoptosis assays were performed. The in vivo studies were carried out based on the Chorion Allantois Membrane (CAM) of the fertilized chicken egg. Pharmacokinetics, toxicity as well as tumour proliferation and apoptosis were measured. Results: B associated pathways are involved.kSodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered WRJHWKHUDQWDJRQL]HHᚎHFWVRIHDFKRWKHU)RUWKHLQYLYRVWXGLHVDZDWHUVROXEOH complex 4-HPR with a cyclodextrin was created. A single dose of sodium butyrate DQG+35VKRZHGDSHDNOHYHOLQSODVPDZLWKLQPLQ%RWKFRPSRXQGVLQGXFHG inhibition of proliferation and induced apoptosis in prostate tumour xenografted RQ WKH &$0 $QDO\VLV RI WKH F\WRWR[LF HᚎHFWV RI WKH GUXJV XVHG LQ FRPELQDWLRQ GHPRQVWUDWHGDQDQWDJRQLVWLFHᚎHFWRQLQKLELWLRQRISUROLIHUDWLRQDQGRQLQGXFWLRQ of apoptosis in vivo. Western blot analysis showed that possibly JNK and NFConclusions: These rather unexpected results demonstrate an antagonistic WUHDWPHQW HᚎHFW RI VRGLXP EXW\UDWH DQG +35 0RUH JHQHUDOO\ VSHDNLQJ combinational therapies need to be carefully investigated due to potential DQWDJRQLVWLF HᚎHFWV LQ WKH FOLQLFDO VHWWLQJ GHVSLWH SURPLVLQJ UHVXOWV RI D monotherapeutic.
825 CD-168 AS A POTENTIAL IMMUNOGENIC ANTIGEN IN ADVANCED PROSTATE CANCER DISEASE Kuefer R.1, Greiner J.2, Varambally S., Chinnaiyan A.L., Rubin M.A.4, Schmitt M.2, 5LQJKRᚎHU02 University of Ulm, Dept. of Urology, Ulm, Germany, 2University of Ulm, Dept. of Internal Medicine, Ulm, Germany, University of Michigan, Dept. of Pathology, Ann Arbor, United States of America, 4Cornell University, Dept. of Pathology, New York, United States of America 1
Introduction & Objectives: Treatment options for early stage prostate cancer are well GHᚏQHGDQGORFDOL]HGSURVWDWHFDQFHUFDQEHFXUHGE\VHYHUDOVWUDWHJLHV+RZHYHUWKHUH is tremendous need to identify substances being active in advanced tumour stages as the therapeutic outcome in these cases is still disappointing. One approach is to deliver targeted WKHUDS\ EDVHG RQ LGHQWLᚏHG KXPDQ WXPRXU DQWLJHQV VSHFLᚏFDOO\ H[SUHVVHG LQ QHRSODVWLF tissue and recognised by CD4/CD8 T-cells or antibodies. Material & Methods: We employed serological screening of recombinant expression libraries (SEREX) to identify potential immunological target structures. Consequently, candidate antigens were screened by DNA microarrays consisting of approximately 20K genes, GHVLJQHGWRSURᚏOHEHQLJQDQGPDOLJQDQWSURVWDWHWLVVXHV*HQHVEHLQJRYHUH[SUHVVHGLQ far advanced disease stages on the cDNA level were evaluated on the protein level by tissue microarrays representing various stages of prostate cancer disease including about 900 tissue cores. Protein expression was measured by the Chomavision system. Results: %\6(5(;JHQHVZLWKSRWHQWLDOKXPRUDOUHVSRQVHFRXOGEHLGHQWLᚏHGRIWKH WDUJHWVLGHQWLᚏHGE\6(5(;VKRZHGDVLJQLᚏFDQWRYHUH[SUHVVLRQRQWKHNF'1$DUUD\ in localized prostate cancer compared to benign prostatic hyperplasia and in metastases FRPSDUHG WR ORFDOL]HG SURVWDWH FDQFHU 2QH JHQH ZKLFK KDV EHHQ LGHQWLᚏHG HDUOLHU DV an immunogenic antigen in acute and chronic leukemias by our group, CD168, showed D KLJKO\ VLJQLᚏFDQW RYHU H[SUHVVLRQ LQ SURVWDWH FDQFHU PHWDVWDVHV FRPSDUHG WR ORFDOL]HG disease (p=0.007). On the protein level CD168 was highest in metastatic tissue samples DQGVLJQLᚏFDQWO\KLJKHULQQHRSODVWLFORFDOL]HGGLVHDVHFRPSDUHGWREHQLJQWLVVXH S Interestingly, high CD168 expression had an association to clinical parameters known to be associated with better clinical outcome. Patients with high CD168 expression in the SULPDULHVKDGDVLJQLᚏFDQWO\ORZHUULVNIRUELRFKHPLFDOIDLOXUH ORJUDQNS 55 In cell culture experiments, the number of viable cells was reduced in blocking experiments XVLQJKRUPRQHVHQVLWLYH /1&D3 DQGKRUPRQHLQVHQVLWLYHPHWDVWDWLF 3&DQG'8 prostate cancer cell lines. Conclusions: $FNQRZOHGJLQJWKHSURYHQLPPXQRJHQLFHᚎHFWVRI&'LQOHXNHPLDWKLV antigen is intriguing as a therapeutic target in far advanced prostate cancer disease.
826 IS THERE A CORRELATION BETWEEN IMMUNE RESPONSE WITHIN THE TUMOUR AND PSA PROGRESSION FREE SURVIVAL FOLLOWING RRP IN PATIENTS WITH CLINICALLY LOCALISED PROSTATE CANCER? Prayer-Galetti T.1, Viola A.2, Gardiman M., Betto G.1, Bronte V.4, Pagano F.1 Clinic Urologica, Dept. of Urology of Padua, Padua, Italy, 2Venetian Institute for Molecular Medicine, Padua, Italy, University di Padua, Dept. of Pathology Padua, Padua, Italy, 4Institute Oncology Veneto, Padua, Italy
1
Introduction & Objectives: +XPDQ3URVWDWLF$GHQRFDUFLQRPDV 3& DUHLQᚏOWUDWHGE\ WHUPLQDOO\GLᚎHUHQWLDWHGF\WRWR[LF7O\PSKRF\WHV&RUUHODWLRQEHWZHHQORFDOLPPXQH response and clinical outcome is still unknown. To identify if immune response within the tumor relates to patients PSA progression free survival (PFS) following radical retropubic prostatectomy (RRP) for clinically localized PC. Material & Methods: Tissue samples were obtained from surgical specimens of 21 previously untreated patients who underwent RRP for clinically localized PC. Immediately after the surgery, prostate specimens were processed by the pathologist and sent to the laboratory. Samples were analyzed by FACS (BD Biosciences) analysis and immunohistochemistry to determine phenotype of T-lymphocytes LQᚏOWUDWLQJ3&7XPRXUVZHUHVWDJHGDFF8,&&710DQGJUDGHGDFF*OHDVDRQ Score. Patients following surgery were not treated till PSA progression (PSA> 0.4 ng/ ml). Clinical and pathological data were prospectively entered in a data base. Median SDWLHQWV IROORZXS LV PRQWKV UDQJH 6WDWLVWLFDO WHVWLQJ PHWKRGV ZHUH based on the nonparametric combination of dependent permutation tests. In addition, conditional testing inferences were adopted. Results: ,Q 3& VDPSOHV WXPRXU 7,/ LQᚏOWUDWLQJ ZHUH PDLQO\ &' 7 O\PSKRF\WHV &'7,/ZHUHHLWKHU&&5&'5$&'/ HᚎHFWRUPHPRU\SKHQRW\SH RU&&5 &'5$ &'/ WHUPLQDOO\ GLᚎHUHQWLDWHG &7/ 3YDOXH DGMXVWHG IRU PXOWLSOLFLW\ (p-FEW) shows that DFS correlated with preoperatory PSA (p-FEW: 0.080) and SURVWDWH FDSVXOH LQYDVLRQ S)(: $OWKRXJK &' &' &'DQG &' FRUUHODWHGZLWKLQHDFKRWKHU S)(: ದ WKH\GLGQRWFRUUHODWHZLWK')6 Conclusions: Our study demonstrated no correlation between immune response within the tumor and PSA progression free survival following RRP for clinically localized PC.
Eur Urol Suppl 2008;7(3):277
824
CARBON NANOTUBES: A NANOCONTAINER MEDIATES TRANSPORT OF CHEMOTHERAPEUTICS
ANTAGONISTIC EFFECTS OF SODIUM BUTYRATE AND N-(4HYDROXYPHENYL)RETINAMIDE ON PROSTATE CANCER
Kunze D.1, Hampel S.2, Kraemer K.1, Haase D.2, Fuessel S.1, Leonhardt A.2, Meye A.1, Buechner B.2, Grimm M.O.1, Wirth M.P.1
Kuefer R.1, Genze F.1, Zugmaier W.2, Rinnab L.1, Hautmann R.E.2, Buechele B.2
Technical University of Dresden, Dept. of Urology, Dresden, Germany, 2Institute for Solid State and Materials Research, IFW, Dresden, Germany 1
Introduction & Objectives: Multiwalled carbon nanotubes (CNTs) are cylindrical structures with 40-60 nm in diameter and a few µm in length. Their hollow core is surrounded by various carbon shells. CNTs are characterized by a high aspect ration and high mechanical and FKHPLFDOVWDELOLW\7KHLUH[WUDRUGLQDU\SURSHUWLHVPDNH&17VLQWHUHVWLQJWRROVIRUDZLGHᚏHOG of applications, e.g. in material sciences, biology and medicine. The aim of the present study was the development of a nano-scaled container for drug delivery. Therefore, an approach IRU ᚏOOLQJ RI &17V E\ SODWLQXPEDVHG FKHPRWKHUDSHXWLF GUXJV ZDV GHYHORSHG DQG WKHLU F\WRWR[LFHᚎHFWVZHUHWHVWHGLQDFHOOFXOWXUHPRGHO Material & Methods: CNTs were synthesized by chemical vapouB, Dept. of ur deposition (CVD) with iron as catalyst in a solid source CVD-system. A liquid phase method using water DV VROYHQW ZDV XVHG WR ᚏOO &17V ZLWK FDUERSODWLQ RU FLVSODWLQ &7&17V +XPDQ VHUXP DOEXPLQ PHGLDWHG WKH GLVSHUVLRQ RI QDWXUDOO\ K\GURSKRELF &17V LQ SKRVSKDWH EXᚎHUHG saline. The amount of platinum that can be transported by CT-CNTs and release kinetics ZHUHTXDQWLᚏHGE\DWRPLFDEVRUSWLRQVSHFWURVFRS\7KHSURVWDWHFDQFHUFHOOOLQHV3&DQG '8 ZHUH WUHDWHG ZLWK GLᚎHUHQW FRQFHQWUDWLRQV RI HPSW\ &17V GUXJ ᚏOOHG &7&17V RU free drug, respectively. After incubation for 24h, cells were washed and incubated in fresh medium until examination of cellular viability (WST-1 assay), cell count, apoptosis (annexin V staining) and cell cycle distribution. Results: Empty CNTs did not alter the growth features of neither tumour cells nor nonPDOLJQDQWᚏEUREODVWVXQGHUWKHFRQGLWLRQVWHVWHG)XUWKHUPRUHWKHFHOOXODUXSWDNHRI&17V ZDVFRQᚏUPHG$IWHUV\QWKHVLVHPSW\&17VFRXOGEHUHRSHQHGDQGᚏOOHGZLWKFDUERSODWLQ DQG FLVSODWLQ 7KH SODWLQXP ᚏOOLQJ ZDV FOHDUO\ YLVLEOH DV EODFN GRWV LQVLGH RI &7&17V E\ PHDQVRIWUDQVPLVVLRQHOHFWURQPLFURVFRS\$ᚏOOLQJ\LHOGRIDERXW ZZ ZDVUHDFKHG CT-CNTs have been shown to release the incorporated drugs in the culture medium within K7KHHᚎHFWLYHQHVVRIWKHFKHPRWKHUDSHXWLFDIWHUUHOHDVHIURP&7&17VZDVVKRZQLQ cell culture experiments. CT-CNTs induced a concentration-dependent inhibition of viability, reduced cell numbers, induced apoptosis and caused a cell cycle arrest in G2/M. Conclusions: 7KLV SUHOLPLQDU\ VWXG\ GHVFULEHV WKH V\QWKHVLV DQG IXQFWLRQ RI &17V ᚏOOHG with chemotherapeutic drugs. These potential nanocontainers for drug delivery are nonWR[LFE\WKHPVHOYHVFDQEHᚏOOHGZLWKGUXJVDQGUHOHDVHWKHPRYHUWLPHWRSURPRWHSRWHQW DQWLSUROLIHUDWLYHHᚎHFWVRQSURVWDWHFDQFHUFHOOV
1 University of Ulm, Dept. of Urology, Ulm, Germany, 2University of Ulm, Dept. of Pharmacology and Natural Products, Ulm, Germany
Introduction & Objectives: Butyrates and retinoids are promising agents for the treatment of various tumours. In prostate cancer both drugs have demonstrated antineoplastic activity. In this study we set out to analyse a combinational WUHDWPHQW H[SHFWLQJ DQ DGGLWLYH WUHDWPHQW HᚎHFW ZLWK OHVV VLGH HᚎHFWV GXH WR reduced dosages of the single drugs. Material & Methods: 7KH HᚎHFW RI VRGLXP EXW\UDWH DQG 1 K\GUR[\SKHQ\O UHWLQDPLGH +35 RQ SURVWDWH FDQFHU FHOOV 3& DQG /1&D3 DV PRQRWKHUDS\ or in combination was tested in vitro and in vivo. For the in vitro analysis, viability and apoptosis assays were performed. The in vivo studies were carried out based on the Chorion Allantois Membrane (CAM) of the fertilized chicken egg. Pharmacokinetics, toxicity as well as tumour proliferation and apoptosis were measured. Results: B associated pathways are involved.kSodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered WRJHWKHUDQWDJRQL]HHᚎHFWVRIHDFKRWKHU)RUWKHLQYLYRVWXGLHVDZDWHUVROXEOH complex 4-HPR with a cyclodextrin was created. A single dose of sodium butyrate DQG+35VKRZHGDSHDNOHYHOLQSODVPDZLWKLQPLQ%RWKFRPSRXQGVLQGXFHG inhibition of proliferation and induced apoptosis in prostate tumour xenografted RQ WKH &$0 $QDO\VLV RI WKH F\WRWR[LF HᚎHFWV RI WKH GUXJV XVHG LQ FRPELQDWLRQ GHPRQVWUDWHGDQDQWDJRQLVWLFHᚎHFWRQLQKLELWLRQRISUROLIHUDWLRQDQGRQLQGXFWLRQ of apoptosis in vivo. Western blot analysis showed that possibly JNK and NFConclusions: These rather unexpected results demonstrate an antagonistic WUHDWPHQW HᚎHFW RI VRGLXP EXW\UDWH DQG +35 0RUH JHQHUDOO\ VSHDNLQJ combinational therapies need to be carefully investigated due to potential DQWDJRQLVWLF HᚎHFWV LQ WKH FOLQLFDO VHWWLQJ GHVSLWH SURPLVLQJ UHVXOWV RI D monotherapeutic.
825 CD-168 AS A POTENTIAL IMMUNOGENIC ANTIGEN IN ADVANCED PROSTATE CANCER DISEASE Kuefer R.1, Greiner J.2, Varambally S., Chinnaiyan A.L., Rubin M.A.4, Schmitt M.2, 5LQJKRᚎHU02 University of Ulm, Dept. of Urology, Ulm, Germany, 2University of Ulm, Dept. of Internal Medicine, Ulm, Germany, University of Michigan, Dept. of Pathology, Ann Arbor, United States of America, 4Cornell University, Dept. of Pathology, New York, United States of America 1
Introduction & Objectives: Treatment options for early stage prostate cancer are well GHᚏQHGDQGORFDOL]HGSURVWDWHFDQFHUFDQEHFXUHGE\VHYHUDOVWUDWHJLHV+RZHYHUWKHUH is tremendous need to identify substances being active in advanced tumour stages as the therapeutic outcome in these cases is still disappointing. One approach is to deliver targeted WKHUDS\ EDVHG RQ LGHQWLᚏHG KXPDQ WXPRXU DQWLJHQV VSHFLᚏFDOO\ H[SUHVVHG LQ QHRSODVWLF tissue and recognised by CD4/CD8 T-cells or antibodies. Material & Methods: We employed serological screening of recombinant expression libraries (SEREX) to identify potential immunological target structures. Consequently, candidate antigens were screened by DNA microarrays consisting of approximately 20K genes, GHVLJQHGWRSURᚏOHEHQLJQDQGPDOLJQDQWSURVWDWHWLVVXHV*HQHVEHLQJRYHUH[SUHVVHGLQ far advanced disease stages on the cDNA level were evaluated on the protein level by tissue microarrays representing various stages of prostate cancer disease including about 900 tissue cores. Protein expression was measured by the Chomavision system. Results: %\6(5(;JHQHVZLWKSRWHQWLDOKXPRUDOUHVSRQVHFRXOGEHLGHQWLᚏHGRIWKH WDUJHWVLGHQWLᚏHGE\6(5(;VKRZHGDVLJQLᚏFDQWRYHUH[SUHVVLRQRQWKHNF'1$DUUD\ in localized prostate cancer compared to benign prostatic hyperplasia and in metastases FRPSDUHG WR ORFDOL]HG SURVWDWH FDQFHU 2QH JHQH ZKLFK KDV EHHQ LGHQWLᚏHG HDUOLHU DV an immunogenic antigen in acute and chronic leukemias by our group, CD168, showed D KLJKO\ VLJQLᚏFDQW RYHU H[SUHVVLRQ LQ SURVWDWH FDQFHU PHWDVWDVHV FRPSDUHG WR ORFDOL]HG disease (p=0.007). On the protein level CD168 was highest in metastatic tissue samples DQGVLJQLᚏFDQWO\KLJKHULQQHRSODVWLFORFDOL]HGGLVHDVHFRPSDUHGWREHQLJQWLVVXH S Interestingly, high CD168 expression had an association to clinical parameters known to be associated with better clinical outcome. Patients with high CD168 expression in the SULPDULHVKDGDVLJQLᚏFDQWO\ORZHUULVNIRUELRFKHPLFDOIDLOXUH ORJUDQNS 55 In cell culture experiments, the number of viable cells was reduced in blocking experiments XVLQJKRUPRQHVHQVLWLYH /1&D3 DQGKRUPRQHLQVHQVLWLYHPHWDVWDWLF 3&DQG'8 prostate cancer cell lines. Conclusions: $FNQRZOHGJLQJWKHSURYHQLPPXQRJHQLFHᚎHFWVRI&'LQOHXNHPLDWKLV antigen is intriguing as a therapeutic target in far advanced prostate cancer disease.
826 IS THERE A CORRELATION BETWEEN IMMUNE RESPONSE WITHIN THE TUMOUR AND PSA PROGRESSION FREE SURVIVAL FOLLOWING RRP IN PATIENTS WITH CLINICALLY LOCALISED PROSTATE CANCER? Prayer-Galetti T.1, Viola A.2, Gardiman M., Betto G.1, Bronte V.4, Pagano F.1 Clinic Urologica, Dept. of Urology of Padua, Padua, Italy, 2Venetian Institute for Molecular Medicine, Padua, Italy, University di Padua, Dept. of Pathology Padua, Padua, Italy, 4Institute Oncology Veneto, Padua, Italy
1
Introduction & Objectives: +XPDQ3URVWDWLF$GHQRFDUFLQRPDV 3& DUHLQᚏOWUDWHGE\ WHUPLQDOO\GLᚎHUHQWLDWHGF\WRWR[LF7O\PSKRF\WHV&RUUHODWLRQEHWZHHQORFDOLPPXQH response and clinical outcome is still unknown. To identify if immune response within the tumor relates to patients PSA progression free survival (PFS) following radical retropubic prostatectomy (RRP) for clinically localized PC. Material & Methods: Tissue samples were obtained from surgical specimens of 21 previously untreated patients who underwent RRP for clinically localized PC. Immediately after the surgery, prostate specimens were processed by the pathologist and sent to the laboratory. Samples were analyzed by FACS (BD Biosciences) analysis and immunohistochemistry to determine phenotype of T-lymphocytes LQᚏOWUDWLQJ3&7XPRXUVZHUHVWDJHGDFF8,&&710DQGJUDGHGDFF*OHDVDRQ Score. Patients following surgery were not treated till PSA progression (PSA> 0.4 ng/ ml). Clinical and pathological data were prospectively entered in a data base. Median SDWLHQWV IROORZXS LV PRQWKV UDQJH 6WDWLVWLFDO WHVWLQJ PHWKRGV ZHUH based on the nonparametric combination of dependent permutation tests. In addition, conditional testing inferences were adopted. Results: ,Q 3& VDPSOHV WXPRXU 7,/ LQᚏOWUDWLQJ ZHUH PDLQO\ &' 7 O\PSKRF\WHV &'7,/ZHUHHLWKHU&&5&'5$&'/ HᚎHFWRUPHPRU\SKHQRW\SH RU&&5 &'5$ &'/ WHUPLQDOO\ GLᚎHUHQWLDWHG &7/ 3YDOXH DGMXVWHG IRU PXOWLSOLFLW\ (p-FEW) shows that DFS correlated with preoperatory PSA (p-FEW: 0.080) and SURVWDWH FDSVXOH LQYDVLRQ S)(: $OWKRXJK &' &' &'DQG &' FRUUHODWHGZLWKLQHDFKRWKHU S)(: ದ WKH\GLGQRWFRUUHODWHZLWK')6 Conclusions: Our study demonstrated no correlation between immune response within the tumor and PSA progression free survival following RRP for clinically localized PC.
Eur Urol Suppl 2008;7(3):277