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MRNA EXPRESSION LEVELS AND PROGNOSTIC VALUE OF 40 ANGIOGENIC GENES IN A LARGE SERIES OF 157 BLADDER TUMOURS
887 C-ERB-B2, AURORA-A, MIB-1 AND P53 HAVE PREDICTIVE VALUE FOR VASCULAR INVASION AND RELAPSE IN UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMAS Comperat E.1, Roupret M.2, Chartier-Kastler E.2, Bitker M-O.2, Capron F.1, Camparo P., Richard F.2, Cussenot O.4
888 DETECTION OF IMMUNE RESPONSES AGAINST URINARY BLADDER CANCER IN SENTINEL LYMPH NODES Sherif A.1, Marits P.2, Karlsson M.2, Garske U., Thorn M.4, Winqvist O.2 1
Karolinska University Hospital, Dept. of Urology, Stockholm, Sweden, Karolinska University Hospital, Dept. of Medicine, Unit of Clinical Allergy Research, Stockholm, Sweden, Uppsala University Hospital, Dept. of Medical Sciences, Nuclear Medicine, Uppsala University Hospital, Sweden, Uppsala, Sweden, 4South Stockholm General Hospital, Dept. of Surgery, Stockholm, Sweden
2
+RSLWDO/D3LWL«6DOSHWULªUH$3+38QLYHUVLW«30&3DULV9,'HSWRI3DWKRORJ\3DULV)UDQFH 2 +RSLWDO/D3LWL«6DOSHWULªUH$3+38QLYHUVLW«30&3DULV9,'HSWRI8URORJ\3DULV)UDQFH +RSLWDOGHV,QVWUXFWLRQVGHOಬ$UP«H9DOGH*U¤FH'HSWRI3DWKRORJ\3DULV)UDQFH 4Hopital 7HQRQ$3+38QLYHUVLW«30&3DULV9,'HSWRI8URORJ\3DULV)UDQFH 1
Introduction & Objectives: Upper urinary tract transitional cell carcinomas (UUT-TCC) are rare but aggressive. Today’s main prognostic factors are tumor stage and grade. Vascular invasion, a factor for predicting relapse and metastatic disease is not always seen on surgical SDUDᚑQ HPEHGGHG VDPSOHV DOWKRXJK WKH\ PLJKW EH SUHVHQW :H ZDQWHG WR HYDOXDWH DQ LPPXQRKLVWRFKHPLFDOSURᚏOHWREHDEOHWRSUHGLFWYDVFXODULQYDVLRQDQGUHODSVHLQ8877&& Material & Methods: 41 patients with UUT-TCC have been explored. 18 had ureteral localisation, LQWKHUHQDOSHOYLV S7DORZJUDGHWXPRXUVDQGS7DKLJKJUDGHWXPRXUVS7S7 S7DQGS7 ,PPXQRKLVWRFKHPLVWU\IRUFHUEE$XURUD$SDQG0,%ZDVSHUIRUPHG on tissue micro arrays taken from surgical specimen of all these patients. Fluorescence in situ hybridization (FISH) was made on samples with immunohistochemical overexpression. Results: Patients were aged from 46 to 100 years (mean 70.6 a). Eleven patients (27%) showed DVVRFLDWLRQZLWKFDUFLQRPDLQVLWX RISDWLHQWVGLVSOD\HGYDVFXODULQYDVLRQLQVXUJLFDO VSHFLPHQ GHYHORSHG UHODSVH GLHG RI GLVHDVH 9DVFXODU LQYDVLRQ ZDV DVVRFLDWHGZLWKRYHUH[SUHVVLRQRIFHUEE S $XURUD$ S S DQG MIB-1 (0.0017). Relapse was associated with high expression of c-erb-b2 (p= 0.019), Aurora-A S 0,% DQGS FHUEEUHVXOWVKDYHEHHQFRQᚏUPHGE\),6+ Conclusions: Independent prognostic factors of vascular invasion and relapse in UUT-TCC are important to be established. Immunohistochemistry is easily available in pathologists daily URXWLQHDQGLWLVLPSRUWDQWWRᚏQGSURᚏOHVRQSURWHLQOHYHOWRSUHGLFWEDGFOLQLFDORXWFRPHIRUD better patient’s follow-up. c-erb-2 is an important prognostic factor and its overexpression has been observed in high grade and high stade bladder tumours. Few data are available on UUTTCC, our study demonstrates clearly implication of this molecule. Aurora-A plays a role in cell division and in maintaining genomic integrity. It is linked to clinical aggressiveness and poor RYHUDOOVXUYLYDORIWKHSDWLHQWVLQEODGGHUFDQFHU2XUVWXG\LVWKHᚏUVWWRVKRZLPSOLFDWLRQLQ8&& 7&&0DMRULPSOLFDWLRQSDQG0,%LQ8&&7&&DUHNQRZQWREHSURJQRVWLFIDFWRUVRIEDG FOLQLFDORXWFRPH2XUGDWDFRQᚏUPWKHVHᚏQGLQJVRIWKHOLWHUDWXUH:HSURSRVHDQLPPXQRSURᚏOH RI FHUEE $XURUD$ S DQG 0,% WR SUHGLFW YDVFXODU LQYDVLRQ DQG UHODSVH LQ 8&&7&& considering that each marker has predictive power.
Introduction & Objectives: The lymphatic drainage from a tumour is received in the sentinel node where the immune system encounters tumour derived antigens. We investigated anti-tumoural lymphocyte function in sentinel nodes from patients with urinary bladder cancer. Material & Methods: In 14 patients undergoing cystectomy due to bladder cancer, radioactive tracer and blue dye were used to identify the sentinel node. Cell suspensions from the tumour, sentinel- and non-sentinel nodes DQGSHULSKHUDOEORRGZHUHDQDO\]HGE\ᚐRZF\WRPHWU\ZLWKDQWLERGLHVDJDLQVW lymphocyte surface antigens and against the tumour cell marker cytokeratin-20. Reactivity against autologous tumour extract and the mitogen Concanavalin A ZDVWHVWHGLQSUROLIHUDWLRQDVVD\VZLWK+7K\PLGLQHLQFRUSRUDWLRQ/\PSKRF\WHV were put in long-term culture with IL-2 and autologous tumour extract. Results: Sentinel nodes were detected in 12 of the 14 patients. Antigen dependent proliferation in response to autologous tumour extract was detected in 6 patients, in 5 cases in sentinel nodes, in the remaining case in a non-sentinel node. Proliferation against Concanavalin A was vigorous in lymph nodes from DOO SDWLHQWV ZKHUHDV WXPRXU LQᚏOWUDWLQJ O\PSKRF\WHV ZHUH XQUHVSRQVLYH Lymphocytes from sentinel nodes could be expanded in vitro. Conclusions: Tumour reactive lymphocytes are present in sentinel nodes draining human bladder cancers. These cells display immunologic function upon restimulation in vitro, and provide a possible source for expansion and subsequent adoptive T cell immunotherapy.
889
890
DECREASED MASPIN PROTEIN CORRELATES WITH TUMOUR PROGRESSION AND RECURRENCE IN TRANSITIONAL CELL CARCINOMA
MRNA EXPRESSION LEVELS AND PROGNOSTIC VALUE OF 40 ANGIOGENIC GENES IN A LARGE SERIES OF 157 BLADDER TUMOURS
Kramer M.W.1, Kuczyk M.A.1, Hennenlotter J1, Kruck S1, Garcia A2, Stenzl A1, Merseburger A.S.1
Pignot G.1, Bieche I.2, Vacher S.2, Lidereau R.2, Debre B.1, Amsellem-Ouazana D.1 Cochin Hospital, Dept. of Urology, Paris, France, 2&HQWUH 5HQ« +XJXHQLQ 'HSW RI Oncogenetic, Saint-Cloud, France
1
Eberhard-Karls-University, Dept. of Urology, Tübingen, Germany, 2Miller School of Medicine, Florida Histopathology Services, Miami, United States of America
1
Introduction & Objectives: Maspin is a 42kDa protein that belongs to the family of serine protease inhibitors. It is involved in various cell and matrix related processes such as cell adhesion, apoptosis, inhibition of cell motility, invasion and angiogenesis. In cancer tissue, 0DVSLQZDVIRXQGWRLQᚐXHQFHDQJLRJHQHVLVWXPRUJURZWKPHWDVWDVLVDQGWKHSURJQRVLV of tumor patients. The role of Maspin in bladder cancer is controversially discussed. This study was performed to further analyze the involvement of this serpin protease in transitional cell carcinoma of the bladder (TCC) as well as its prognostic impact. Material & Methods: A cohort of 182 bladder cancer specimens (pTa: 87, pT1: 71, pT2-4: 22) from patients with muscle and non-muscle invasive disease on whom there is DPLQLPXP\HDUIROORZXSZDVLQFOXGHGLQWKHVWXG\7KHVSHFLPHQVZHUHVWDLQHGIRU Maspin using the tissue microarrays (TMA) and immunohistochemistry techniques. Each WLVVXHVSHFLPHQZDVDVVHVVHGRQDVWDLQLQJVFDOHUDQJLQJEHWZHHQ QRVWDLQLQJ WR (strong staining). Results: &RPELQHG H[SUHVVLRQ OHYHOV S7DS7 ZHUH VLJQLᚏFDQWO\ LQFUHDVHG FRPSDUHG WR PXVFOH LQYDVLYH VSHFLPHQV S :LWK DV WKH FXWRᚎ OLPLW 0DVSLQ VWDLQLQJ SUHGLFWHG SURJUHVVLRQ ZLWK D VHQVLWLYLW\ RI DQG D VSHFLᚏFLW\ RI S ,Q SUHGLFWLQJ UHFXUUHQFH 0DVSLQ VWDLQLQJ VKRZHG VHQVLWLYLW\ DQG VSHFLᚏFLW\ XVLQJ WKH VDPH FXWRᚎ OLPLW S 3HUIRUPLQJ .DSODQ0HLHU DQDO\VHV ORZ 0DVSLQ protein expression (staining score <175) was correlated with a higher incidence of tumor progression (p<0.0001). However, expression levels of Maspin protein did not distinguish between pTa and pT1 specimens. Multivariate analyses indicated Maspin expression as an LQGHSHQGHQWIDFWRUIRUSUHGLFWLQJERWKSURJUHVVLRQ S DQGUHFXUUHQFH S Conclusions: In this study, the protein expression of Maspin, a tumor suppressor, was VLJQLᚏFDQWO\XSUHJXODWHGZLWKFRQVHFXWLYHKLJKHUVWDJHV$QDO\VHVSHUIRUPHGRQIROORZXS data showed increased expression levels with an increased occurrence of progression. The present results suggest that Maspin protein expression is an independent prognostic indicator for predicting recurrence and progression. This study further emphasizes a possible clinical role of this novel tumor suppressor gene in TCC.
Introduction & Objectives: During carcinogenesis, angiogenesis is a fundamental process allowing both tumour growth and metastatic spread. Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, anti-angiogenic molecules could also add to already existing treatment options. The aim of this study was to evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a prognostic implication. Material & Methods: Expression levels of 40 genes involved in angiogenesis were assessed by quantitative real time RT-PCR in normal and tumoural human bladder samples. Tumours ZHUH REWDLQHG IURP SDWLHQWV ZRPHQ DQG PHQ PHDQ DJH \HDUV ZKR underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. $OOSDWLHQWVVLJQHGDQLQIRUPHGFRQVHQW3DWKRORJLFDOWXPRXUVWDJLQJVKRZHG VXSHUᚏFLDO 7&& ORZ JUDGH S7D JURXS ,, KLJK JUDGH S7D JURXS ,,, DQG KLJK JUDGH S7 JURXS,9 DQGPXVFOHLQYDVLYHWXPRXUVDOORIKLJKJUDGH ุS7JURXS9 Results: 9(*)$ 0(7 &;&5 DQG ,/ ZHUH VLJQLᚏFDQWO\ RYHU H[SUHVVHG LQ WXPRXU samples as compared to normal bladder tissue (p<0.01). VEGFA over expressions were ERWKVLJQLᚏFDQWLQVXSHUᚏFLDODQGLQYDVLYHWXPRXUVDPSOHVDVFRPSDUHGWRQRUPDOEODGGHU WLVVXH S 0(7 P51$ RYHU H[SUHVVLRQV ZHUH VLJQLᚏFDQW ZKHQ FRPSDULQJ ORZ grade pTa tumours to normal bladder samples (p<0.01), whereas IL8 and CXCR4 over H[SUHVVLRQV ZHUH VLJQLᚏFDQW ZKHQ FRPSDULQJ DJJUHVVLYH WXPRXUV S7 RU LQYDVLYH WR pTa tumours (p<0.01). In univariate analysis VEGFA over expression is associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively). Multivariate analysis retained T stage, N status, and VEGFA over expression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04 respectively for VEGFA). Conclusions: Our results suggest a major role for several pro-angiogenic genes in bladder carcinogenesis. There is therefore a potential interest of anti-angiogenic targeted therapies in bladder cancer especially those steered against VEGFA. This study shows that VEGFA status could be used as a prognostic factor at the individual level, and as a guide for rationalized use of the costly anti-angiogenic targeted therapies.
Eur Urol Suppl 2008;7(3):293
888 DETECTION OF IMMUNE RESPONSES AGAINST URINARY BLADDER CANCER IN SENTINEL LYMPH NODES Sherif A.1, Marits P.2, Karlsson M.2, Garske U., Thorn M.4, Winqvist O.2 1
Karolinska University Hospital, Dept. of Urology, Stockholm, Sweden, Karolinska University Hospital, Dept. of Medicine, Unit of Clinical Allergy Research, Stockholm, Sweden, Uppsala University Hospital, Dept. of Medical Sciences, Nuclear Medicine, Uppsala University Hospital, Sweden, Uppsala, Sweden, 4South Stockholm General Hospital, Dept. of Surgery, Stockholm, Sweden
2
+RSLWDO/D3LWL«6DOSHWULªUH$3+38QLYHUVLW«30&3DULV9,'HSWRI3DWKRORJ\3DULV)UDQFH 2 +RSLWDO/D3LWL«6DOSHWULªUH$3+38QLYHUVLW«30&3DULV9,'HSWRI8URORJ\3DULV)UDQFH +RSLWDOGHV,QVWUXFWLRQVGHOಬ$UP«H9DOGH*U¤FH'HSWRI3DWKRORJ\3DULV)UDQFH 4Hopital 7HQRQ$3+38QLYHUVLW«30&3DULV9,'HSWRI8URORJ\3DULV)UDQFH 1
Introduction & Objectives: Upper urinary tract transitional cell carcinomas (UUT-TCC) are rare but aggressive. Today’s main prognostic factors are tumor stage and grade. Vascular invasion, a factor for predicting relapse and metastatic disease is not always seen on surgical SDUDᚑQ HPEHGGHG VDPSOHV DOWKRXJK WKH\ PLJKW EH SUHVHQW :H ZDQWHG WR HYDOXDWH DQ LPPXQRKLVWRFKHPLFDOSURᚏOHWREHDEOHWRSUHGLFWYDVFXODULQYDVLRQDQGUHODSVHLQ8877&& Material & Methods: 41 patients with UUT-TCC have been explored. 18 had ureteral localisation, LQWKHUHQDOSHOYLV S7DORZJUDGHWXPRXUVDQGS7DKLJKJUDGHWXPRXUVS7S7 S7DQGS7 ,PPXQRKLVWRFKHPLVWU\IRUFHUEE$XURUD$SDQG0,%ZDVSHUIRUPHG on tissue micro arrays taken from surgical specimen of all these patients. Fluorescence in situ hybridization (FISH) was made on samples with immunohistochemical overexpression. Results: Patients were aged from 46 to 100 years (mean 70.6 a). Eleven patients (27%) showed DVVRFLDWLRQZLWKFDUFLQRPDLQVLWX RISDWLHQWVGLVSOD\HGYDVFXODULQYDVLRQLQVXUJLFDO VSHFLPHQ GHYHORSHG UHODSVH GLHG RI GLVHDVH 9DVFXODU LQYDVLRQ ZDV DVVRFLDWHGZLWKRYHUH[SUHVVLRQRIFHUEE S $XURUD$ S S DQG MIB-1 (0.0017). Relapse was associated with high expression of c-erb-b2 (p= 0.019), Aurora-A S 0,% DQGS FHUEEUHVXOWVKDYHEHHQFRQᚏUPHGE\),6+ Conclusions: Independent prognostic factors of vascular invasion and relapse in UUT-TCC are important to be established. Immunohistochemistry is easily available in pathologists daily URXWLQHDQGLWLVLPSRUWDQWWRᚏQGSURᚏOHVRQSURWHLQOHYHOWRSUHGLFWEDGFOLQLFDORXWFRPHIRUD better patient’s follow-up. c-erb-2 is an important prognostic factor and its overexpression has been observed in high grade and high stade bladder tumours. Few data are available on UUTTCC, our study demonstrates clearly implication of this molecule. Aurora-A plays a role in cell division and in maintaining genomic integrity. It is linked to clinical aggressiveness and poor RYHUDOOVXUYLYDORIWKHSDWLHQWVLQEODGGHUFDQFHU2XUVWXG\LVWKHᚏUVWWRVKRZLPSOLFDWLRQLQ8&& 7&&0DMRULPSOLFDWLRQSDQG0,%LQ8&&7&&DUHNQRZQWREHSURJQRVWLFIDFWRUVRIEDG FOLQLFDORXWFRPH2XUGDWDFRQᚏUPWKHVHᚏQGLQJVRIWKHOLWHUDWXUH:HSURSRVHDQLPPXQRSURᚏOH RI FHUEE $XURUD$ S DQG 0,% WR SUHGLFW YDVFXODU LQYDVLRQ DQG UHODSVH LQ 8&&7&& considering that each marker has predictive power.
Introduction & Objectives: The lymphatic drainage from a tumour is received in the sentinel node where the immune system encounters tumour derived antigens. We investigated anti-tumoural lymphocyte function in sentinel nodes from patients with urinary bladder cancer. Material & Methods: In 14 patients undergoing cystectomy due to bladder cancer, radioactive tracer and blue dye were used to identify the sentinel node. Cell suspensions from the tumour, sentinel- and non-sentinel nodes DQGSHULSKHUDOEORRGZHUHDQDO\]HGE\ᚐRZF\WRPHWU\ZLWKDQWLERGLHVDJDLQVW lymphocyte surface antigens and against the tumour cell marker cytokeratin-20. Reactivity against autologous tumour extract and the mitogen Concanavalin A ZDVWHVWHGLQSUROLIHUDWLRQDVVD\VZLWK+7K\PLGLQHLQFRUSRUDWLRQ/\PSKRF\WHV were put in long-term culture with IL-2 and autologous tumour extract. Results: Sentinel nodes were detected in 12 of the 14 patients. Antigen dependent proliferation in response to autologous tumour extract was detected in 6 patients, in 5 cases in sentinel nodes, in the remaining case in a non-sentinel node. Proliferation against Concanavalin A was vigorous in lymph nodes from DOO SDWLHQWV ZKHUHDV WXPRXU LQᚏOWUDWLQJ O\PSKRF\WHV ZHUH XQUHVSRQVLYH Lymphocytes from sentinel nodes could be expanded in vitro. Conclusions: Tumour reactive lymphocytes are present in sentinel nodes draining human bladder cancers. These cells display immunologic function upon restimulation in vitro, and provide a possible source for expansion and subsequent adoptive T cell immunotherapy.
889
890
DECREASED MASPIN PROTEIN CORRELATES WITH TUMOUR PROGRESSION AND RECURRENCE IN TRANSITIONAL CELL CARCINOMA
MRNA EXPRESSION LEVELS AND PROGNOSTIC VALUE OF 40 ANGIOGENIC GENES IN A LARGE SERIES OF 157 BLADDER TUMOURS
Kramer M.W.1, Kuczyk M.A.1, Hennenlotter J1, Kruck S1, Garcia A2, Stenzl A1, Merseburger A.S.1
Pignot G.1, Bieche I.2, Vacher S.2, Lidereau R.2, Debre B.1, Amsellem-Ouazana D.1 Cochin Hospital, Dept. of Urology, Paris, France, 2&HQWUH 5HQ« +XJXHQLQ 'HSW RI Oncogenetic, Saint-Cloud, France
1
Eberhard-Karls-University, Dept. of Urology, Tübingen, Germany, 2Miller School of Medicine, Florida Histopathology Services, Miami, United States of America
1
Introduction & Objectives: Maspin is a 42kDa protein that belongs to the family of serine protease inhibitors. It is involved in various cell and matrix related processes such as cell adhesion, apoptosis, inhibition of cell motility, invasion and angiogenesis. In cancer tissue, 0DVSLQZDVIRXQGWRLQᚐXHQFHDQJLRJHQHVLVWXPRUJURZWKPHWDVWDVLVDQGWKHSURJQRVLV of tumor patients. The role of Maspin in bladder cancer is controversially discussed. This study was performed to further analyze the involvement of this serpin protease in transitional cell carcinoma of the bladder (TCC) as well as its prognostic impact. Material & Methods: A cohort of 182 bladder cancer specimens (pTa: 87, pT1: 71, pT2-4: 22) from patients with muscle and non-muscle invasive disease on whom there is DPLQLPXP\HDUIROORZXSZDVLQFOXGHGLQWKHVWXG\7KHVSHFLPHQVZHUHVWDLQHGIRU Maspin using the tissue microarrays (TMA) and immunohistochemistry techniques. Each WLVVXHVSHFLPHQZDVDVVHVVHGRQDVWDLQLQJVFDOHUDQJLQJEHWZHHQ QRVWDLQLQJ WR (strong staining). Results: &RPELQHG H[SUHVVLRQ OHYHOV S7DS7 ZHUH VLJQLᚏFDQWO\ LQFUHDVHG FRPSDUHG WR PXVFOH LQYDVLYH VSHFLPHQV S :LWK DV WKH FXWRᚎ OLPLW 0DVSLQ VWDLQLQJ SUHGLFWHG SURJUHVVLRQ ZLWK D VHQVLWLYLW\ RI DQG D VSHFLᚏFLW\ RI S ,Q SUHGLFWLQJ UHFXUUHQFH 0DVSLQ VWDLQLQJ VKRZHG VHQVLWLYLW\ DQG VSHFLᚏFLW\ XVLQJ WKH VDPH FXWRᚎ OLPLW S 3HUIRUPLQJ .DSODQ0HLHU DQDO\VHV ORZ 0DVSLQ protein expression (staining score <175) was correlated with a higher incidence of tumor progression (p<0.0001). However, expression levels of Maspin protein did not distinguish between pTa and pT1 specimens. Multivariate analyses indicated Maspin expression as an LQGHSHQGHQWIDFWRUIRUSUHGLFWLQJERWKSURJUHVVLRQ S DQGUHFXUUHQFH S Conclusions: In this study, the protein expression of Maspin, a tumor suppressor, was VLJQLᚏFDQWO\XSUHJXODWHGZLWKFRQVHFXWLYHKLJKHUVWDJHV$QDO\VHVSHUIRUPHGRQIROORZXS data showed increased expression levels with an increased occurrence of progression. The present results suggest that Maspin protein expression is an independent prognostic indicator for predicting recurrence and progression. This study further emphasizes a possible clinical role of this novel tumor suppressor gene in TCC.
Introduction & Objectives: During carcinogenesis, angiogenesis is a fundamental process allowing both tumour growth and metastatic spread. Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, anti-angiogenic molecules could also add to already existing treatment options. The aim of this study was to evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a prognostic implication. Material & Methods: Expression levels of 40 genes involved in angiogenesis were assessed by quantitative real time RT-PCR in normal and tumoural human bladder samples. Tumours ZHUH REWDLQHG IURP SDWLHQWV ZRPHQ DQG PHQ PHDQ DJH \HDUV ZKR underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. $OOSDWLHQWVVLJQHGDQLQIRUPHGFRQVHQW3DWKRORJLFDOWXPRXUVWDJLQJVKRZHG VXSHUᚏFLDO 7&& ORZ JUDGH S7D JURXS ,, KLJK JUDGH S7D JURXS ,,, DQG KLJK JUDGH S7 JURXS,9 DQGPXVFOHLQYDVLYHWXPRXUVDOORIKLJKJUDGH ุS7JURXS9 Results: 9(*)$ 0(7 &;&5 DQG ,/ ZHUH VLJQLᚏFDQWO\ RYHU H[SUHVVHG LQ WXPRXU samples as compared to normal bladder tissue (p<0.01). VEGFA over expressions were ERWKVLJQLᚏFDQWLQVXSHUᚏFLDODQGLQYDVLYHWXPRXUVDPSOHVDVFRPSDUHGWRQRUPDOEODGGHU WLVVXH S 0(7 P51$ RYHU H[SUHVVLRQV ZHUH VLJQLᚏFDQW ZKHQ FRPSDULQJ ORZ grade pTa tumours to normal bladder samples (p<0.01), whereas IL8 and CXCR4 over H[SUHVVLRQV ZHUH VLJQLᚏFDQW ZKHQ FRPSDULQJ DJJUHVVLYH WXPRXUV S7 RU LQYDVLYH WR pTa tumours (p<0.01). In univariate analysis VEGFA over expression is associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively). Multivariate analysis retained T stage, N status, and VEGFA over expression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04 respectively for VEGFA). Conclusions: Our results suggest a major role for several pro-angiogenic genes in bladder carcinogenesis. There is therefore a potential interest of anti-angiogenic targeted therapies in bladder cancer especially those steered against VEGFA. This study shows that VEGFA status could be used as a prognostic factor at the individual level, and as a guide for rationalized use of the costly anti-angiogenic targeted therapies.
Eur Urol Suppl 2008;7(3):293