- Email: [email protected]
MSH2 MUTATIONS AND BLADDER CANCER RISK: FAMILY MEMBERS OF HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (HNPCC) PATIENTS WITH MSH2 MUTATIONS ARE AT INCREASED RISK NOT ONLY FOR UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA (TCC) BUT ALSO BLADDER CANCER
875 INCREASED SEXUAL DYSFUNCTION IN WOMEN WITH LUTS INCLUDING OAB IN A UK GENERAL PRACTICE SETTING: ANALYSES FROM THE THIN DATABASE Vats V.1, Morant S.2, Chapple C., Kelleher C.4 1 3ᚏ]HU,QF'HSWRI2XWFRPHV5HVHDUFK1HZ
Introduction & Objectives: Assess the impact of lower urinary tract symptoms on women’s sexual functioning as reported in a general practice setting. Material & Methods: We conducted a population-based study using The Health Improvement Network 7+,1 GDWDEDVH ZKLFK FRQWDLQV UHFRUGV IURP *3 SUDFWLFHV 5HFRUGHG VH[XDO G\VIXQFWLRQ 6' GLDJQRVLVRIRYHUDFWLYHEODGGHU 2$% VWRUDJHORZHUXULQDU\WUDFWV\PSWRPV /876 LQFOXGLQJXUJHQF\ IUHTXHQF\ XUJHQF\ XULQDU\ LQFRQWLQHQFH DQG QRFWXULD DQG YRLGLQJ /876 LQFOXGLQJ VORZ VWUHDP KHVLWDQF\ VWUDLQLQJ WHUPLQDO GULEEOH LQWHUPLWWHQW VWUHDP VSOLWWLQJ RU VSUD\LQJ ZHUH LGHQWLᚏHG DPRQJ ZRPHQDJHGุ\HDUVEHWZHHQದ Q PLOOLRQRQ Results: The overall prevalence of OAB, storage and voiding LUTS, and SD increased substantially GXULQJWKHVWXG\SHULRGULVLQJIURP FDVHVLQWR FDVHVLQ3UHYDOHQFHRIYRLGLQJ /876LQFUHDVHGIURP FDVHVLQWRLQZKLOH6'LQFUHDVHGIURPWRLQWKH same time period. Incidence of SD in the female LUTS population averaged across the study period (0.128%/year) was twice that of women with no LUTS (0.068%/year). Consequently, prevalence of SD ZDVWLPHVKLJKHUDPRQJZRPHQZLWK/876FRPSDUHGZLWKZRPHQZLWKRXW/876 YV 7KHPHDQDJHIRU/876FDVHVZDVZKLOHPHDQDJHIRU6'ZDV 7KHDGMXVWHGRGGVUDWLR CI) for SD in women with LUTS compared with women with no LUTS was 2.15 (1.77, 2.61) adjusted for age. After passing age 60, the adjusted odds ratio (95% CI) for SD diagnosis compared with the age JURXS \HDUVZDV )LJXUH 7KHDGMXVWHGRGGVUDWLR &, IRU6'LQZRPHQ with OAB was 2.06 (1.92, 2.21). Conclusions: 'HVSLWHWKHGLᚎHUHQFHLQPHDQDJHRISUHYDOHQWFDVHV/876ZHUHDKLJKO\VLJQLᚏFDQW SUHGLFWRURI6'7KHGLᚎHUHQFH in mean age may be the UHVXOW RI GLᚎHUHQFHV LQ VH[XDO activity among age groups. Women with LUTS, including 2$% DUH VLJQLᚏFDQWO\ PRUH likely to report SD compared with those without LUTS/ OAB. These data suggest that the relationship between SD and LUTS/OAB in women should be considered when diagnosing and treating these conditions.
P54 UROTHELIAL TUMOURS: BASIC RESEARCH II Friday, 28 March, 14.00-15.30, Blue Hall 2
876
MSH2 MUTATIONS AND BLADDER CANCER RISK: FAMILY MEMBERS OF HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (HNPCC) PATIENTS WITH MSH2 MUTATIONS ARE AT INCREASED RISK NOT ONLY FOR UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA (TCC) BUT ALSO BLADDER CANCER Skeldon S.1, Semotiuk K.2, Gallinger S.2, Fleshner N., Cotterchio M.2, Jewett M., Zlotta A.4 University of Toronto, Dept. of Urology, Toronto, Canada, 2Mount Sinai Hospital and University of Toronto, Dept. of Gastroenterology, Toronto, Canada, UHN and University of Toronto, Dept. of Urology, Toronto, Canada, 4Mount Sinai Hospital and University of Toronto, Dept. of Urology, Toronto, Canada
1
Introduction & Objectives: We analyzed the risk of bladder cancer and upper tract transitional cell carcinoma (TCC) in patients within families from the Toronto familial colon cancer registry and in particular with MSH2 mutations. Genetic risks for bladder cancer are currently the subject of many investigations. A correlation between hereditary nonpolyposis colorectal cancer and upper tract TCC had been previously described (1) but information about bladder cancer risk in MSH2 mutations within these families is largely unknown. Material & Methods: Cancer data were obtained from the Toronto familial gastrointestinal cancer UHJLVWU\IURP WRLQFOXGLQJSHUVRQVZLWKNQRZQPXWDWLRQV $3&&'+&5$&0/+ MSH6, MYH or FMS2 mutations), among whom 174 had MSH2 mutations. The standardized incidence UDWLRLQ&DQDGD ZHUHXVHGWRPHDVXUHFDQFHUULVNLQRᚎVSULQJVDPRQJIDPLOLHVZLWKSURYHQ06+DQG other mutations according to familial cancer status. Results: :HLGHQWLᚏHGSDWLHQWVZLWKXURWKHOLDOFDQFHUVKDGEODGGHUFDQFHU XSSHU7&& (25%). Thirty-six of these patients had a double primary cancer and 29 (41%) had colon cancer. Among patients with colon cancer, urothelial cancers appeared before colon cancer in 25% of cases. Within the 174 patients in the registry with proven MSH2 mutations, bladder cancer was found in 10 (5.74%) persons but none among the 179 patients with APC, CDH1, CRAC1, MLH1, MSH6, MYH or FMS2 mutations. There were 6 women and 4 men, in contrast with the expected male to female ratio for EODGGHUFDQFHURI LQ&DQDGD 7KLVULVNIRUEODGGHUFDQFHUDPRQJ06+FDUULHUVLVFOHDUO\ increased as compared to the 2.5% and 0.5% lifetime risk among among men and women in Canada, respectively (2). Regarding upper tract TCC among MSH2 carriers, the observed risk was 2.9% (5/174) ZKLFKLVLQOLQHZLWKSUHYLRXVUHSRUWV DERXWWKHVLJQLᚏFDQWO\LQFUHDVHGULVNRIXSSHUWUDFW7&&LQ these populations (1). Conclusions: Siblings of hereditary colorectal cancer patients with MSH2 mutations are at increased risk not only for upper tract TCC as previously demonstrated (which actually can precede the diagnosis of colon cancer) but also of bladder cancer. None of the other genetic markers predisposing to HNPCC was involved in upper tract or bladder cancer TCC. Our study suggests that mutations of mismatch repair proteins may have an important contribution in the development of a subset of TCCs. References 1.Sijmons R.H., Kiemeney L.A., Witjes J.A., Vasen H.F. Urinary tract cancer and hereditary nonpolyposis FRORUHFWDO FDQFHU ULVNV DQG VFUHHQLQJ RSWLRQV - 8URO &DQDGLDQ &DQFHU 6WDWLVWLFV KWWS ZZZQFLFFDQFHUFDYJQLPDJHVSRUWDOFLWB FZB stats_en.pdf
877
878
RESEARCH AND EVALUATION OF NEW MARKERS IN BLADDER CANCER: A PHOSPHOPROTEOMIC STUDY
METHYLATION OF RUNX3 PROMOTER AS A PROMISING PROGNOSTIC MARKER FOR BLADDER TUMOURS
Fiori C.1, Barbero G.2, Giribaldi G.2, Mandili G.2, Destefanis P.1, Ceruti C.1, Bisconti A.1, Carchedi M.T.1, Fontana D.1, Turrini F.2
Kim Y.J.1, Kim T.W.2, Yun S.J.1, Lee H.L.2, Lee S.C.1, Kim W.J.1 1
University of Turin, Dept. of Nefrourologia, Turin, Italy, 2University of Turin, Dept. of Genetica, Biology and Biochimica, Turin, Italy 1
Introduction & Objectives: The most reliable procedure for bladder cancer diagnosis and follow up is cystoscopy with bladder biopsy, this intervention anyway is somewhat invasive DQGH[SDQVLYH7KHLGHQWLᚏFDWLRQRIQHZXULQDU\PDUNHUVFRXOGKDYHDQHQRUPRXVLPSDFW on diagnosis and early treatment of this kind of neoplasm. The discovery of disease markers E\JHQHDQGSURWHLQH[SUHVVLRQSURᚏOLQJWKURXJK'1$PLFURDUUD\DQGSURWHRPLFVSURPLVHV to deliver some solutions to these challenges. However, the activity of protein, that is often UHJXODWHG YLD SRVWWUDQVODWLRQ PRGLᚏFDWLRQV RI ZKLFK SKRVSKRU\ODWLRQ LV RQH RI WKH PRVW prominent, is a more relevant phenotype than its expression during pathogenesis. More than 50% of tyrosine kinases are over expressed or mutated in various human cancers. The aim of this study is to identify new potential bladder cancer protein markers by comparative phospho-proteomic approach for clinical applications. Material & Methods: Bladder cancer samples (5-10 mg) obtained during radical cystectomy or TURB and similar size samples from normal tissues were used. Following extraction proteins were solubilised and separated by 2-DE electrophoresis. Gels obtained were blotted into PVDF membranes and probed with anti-phosphoserine and anti-phosphotyrosine antibody. Afterwards, western-blotting tumoural tissues were compared with normal tissues ,PDJHVDQGGLᚎHUHQWLDOSKRVSKRSURWHLQVZHUHLGHQWLᚏHG,GHQWLᚏFDWLRQVZHUHFDUULHGDIWHU in-gel proteolysis of the electrophoretic spots by MALDI-TOF analysis and peptide mass ᚏQJHUSULQW Results: Tissue samples from patients with histological diagnosis of bladder TCC were analysed. The comparison of serine and tyrosine phosphorylation patterns from healthy DQG FDUFLQRPD WLVVXHV VKRZHG D VLJQLᚏFDQWO\ KLJKHU SKRVSKRU\ODWLRQ VWDWXV LQ FDUFLQRPD WLVVXHV E\VSHFWURPHWULFDQDO\VLVZHLGHQWLᚏHGDERXWWZHQW\SURWHLQVSKRVSKRU\ODWHGRQO\ LQPDOLJQDQWVDPSOHVDQGᚏYHSURWHLQVZLWKXSUHJXODWHGSKRVSKRU\ODWLRQLQFDQFHUWLVVXHV Conclusions: Using minimal amount of tissues from bladder cancer patients and SKRVSKRSURWHRPH DQDO\VLV ZH LGHQWLᚏHG VRPH QHZ SRWHQWLDO SKRVSKRSURWHLQ PDUNHUV 'LDJQRVWLF DQG SURJQRVWLF VLJQLᚏFDQFH RI LGHQWLᚏHG SKRVSKRSURWHLQV ZLOO EH HYDOXDWHG LQ our laboratory in urine samples of healthy and cancer patients. For this purpose we are FUHDWLQJ D SKRVSKRSURWHLQVSHFLᚏF DQWLERG\ FKLS ZKLFK LV RQH RI WKH XOWLPDWH JRDOV IRU routine application of phosphoproteomics in the clinical setting.
Eur Urol Suppl 2008;7(3):290
Chungbuk National University College of Medicine, Dept. of Urology, Cheongju, South Korea, 2Kyung Hee University College of Medicine, Dept. of Urology, Seoul, South Korea Introduction & Objectives: DNA methylation is a key regulator of gene transcription and genomic stability, thus altered DNA methylation is a frequently detected epigenetic change in human cancers. Previously we reported that inactivation of 581; ZKLFK ZDV FDXVHG PDLQO\ E\ HSLJHQHWLF DOWHUDWLRQ ZDV FORVHO\ DVVRFLDWHG ZLWKEODGGHUWXPRXUGHYHORSPHQWVXSHUᚏFLDOUHFXUUHQFHDQGSURJUHVVLRQ7KHDLP RIWKLVVWXG\LVWRHYDOXDWHWKHORQJWHUPIROORZXSUHVXOWVRI581;LQDFWLYDWLRQRQ bladder tumour. Material & Methods: :HXVHGRXUSUHYLRXVO\SXEOLVKHGGDWD &DQFHU5HV IRUPHWK\ODWLRQSDWWHUQVRI581;LQEODGGHUWXPRXUVLQDGGLWLRQWRQHZ GDWDE\PHWK\ODWLRQVSHFLᚏF3&5DQGGLUHFW'1$VHTXHQFLQJ2IWKHVH SDWLHQWV SDWLHQWVIROORZHGSHULRGLFDOO\ZHUHLQFOXGHGLQWKHᚏQDODQDO\VHV0HGLDQIROORZ up period was 49.8 months (1-146). Results: 0HWK\ODWLRQRI581;SURPRWHUZDVIRXQGLQ RI 581; methylation status was not associated with bladder tumour recurrence in long-term IROORZXS 581; PHWK\ODWLRQ ZDV PRUH IUHTXHQWO\ REVHUYHG LQ LQYDVLYH WXPRXUV WKDQ LQ VXSHUᚏFLDO EODGGHU WXPRXUV S 25 &, )XUWKHUPRUH581;PHWK\ODWLRQSDWWHUQVZHUHVLJQLᚏFDQWO\FRUUHODWHGZLWKWXPRXU SURJUHVVLRQ S 25 &, RYHUDOO VXUYLYDO S 25 &, DQG FDQFHUVSHFLᚏF VXUYLYDO S OR: 11.710, 95% CI: 1.510-90.781). Kaplan-Meier estimates also demonstrated VLJQLᚏFDQWGLᚎHUHQFHVLQWXPRXUSURJUHVVLRQ ORJUDQNWHVWS RYHUDOOVXUYLYDO ORJUDQNWHVWS DQGFDQFHUVSHFLᚏFVXUYLYDO ORJUDQNWHVWS E\WKH 581;PHWK\ODWLRQVWDWXV Conclusions: 7KHVH UHVXOWV VWURQJO\ VXJJHVW WKDW LQDFWLYDWLRQ RI 581; GXH WR SURPRWHUPHWK\ODWLRQPLJKWEHDVLJQLᚏFDQWULVNIDFWRUIRULQYDVLYHEODGGHUWXPRXU SURJUHVVLRQRYHUDOOVXUYLYDODQGFDQFHUVSHFLᚏFVXUYLYDO581;PHWK\ODWLRQPD\ be used as a promising marker for assessing prognosis of human bladder tumours.
Introduction & Objectives: Assess the impact of lower urinary tract symptoms on women’s sexual functioning as reported in a general practice setting. Material & Methods: We conducted a population-based study using The Health Improvement Network 7+,1 GDWDEDVH ZKLFK FRQWDLQV UHFRUGV IURP *3 SUDFWLFHV 5HFRUGHG VH[XDO G\VIXQFWLRQ 6' GLDJQRVLVRIRYHUDFWLYHEODGGHU 2$% VWRUDJHORZHUXULQDU\WUDFWV\PSWRPV /876 LQFOXGLQJXUJHQF\ IUHTXHQF\ XUJHQF\ XULQDU\ LQFRQWLQHQFH DQG QRFWXULD DQG YRLGLQJ /876 LQFOXGLQJ VORZ VWUHDP KHVLWDQF\ VWUDLQLQJ WHUPLQDO GULEEOH LQWHUPLWWHQW VWUHDP VSOLWWLQJ RU VSUD\LQJ ZHUH LGHQWLᚏHG DPRQJ ZRPHQDJHGุ\HDUVEHWZHHQದ Q PLOOLRQRQ Results: The overall prevalence of OAB, storage and voiding LUTS, and SD increased substantially GXULQJWKHVWXG\SHULRGULVLQJIURP FDVHVLQWR FDVHVLQ3UHYDOHQFHRIYRLGLQJ /876LQFUHDVHGIURP FDVHVLQWRLQZKLOH6'LQFUHDVHGIURPWRLQWKH same time period. Incidence of SD in the female LUTS population averaged across the study period (0.128%/year) was twice that of women with no LUTS (0.068%/year). Consequently, prevalence of SD ZDVWLPHVKLJKHUDPRQJZRPHQZLWK/876FRPSDUHGZLWKZRPHQZLWKRXW/876 YV 7KHPHDQDJHIRU/876FDVHVZDVZKLOHPHDQDJHIRU6'ZDV 7KHDGMXVWHGRGGVUDWLR CI) for SD in women with LUTS compared with women with no LUTS was 2.15 (1.77, 2.61) adjusted for age. After passing age 60, the adjusted odds ratio (95% CI) for SD diagnosis compared with the age JURXS \HDUVZDV )LJXUH 7KHDGMXVWHGRGGVUDWLR &, IRU6'LQZRPHQ with OAB was 2.06 (1.92, 2.21). Conclusions: 'HVSLWHWKHGLᚎHUHQFHLQPHDQDJHRISUHYDOHQWFDVHV/876ZHUHDKLJKO\VLJQLᚏFDQW SUHGLFWRURI6'7KHGLᚎHUHQFH in mean age may be the UHVXOW RI GLᚎHUHQFHV LQ VH[XDO activity among age groups. Women with LUTS, including 2$% DUH VLJQLᚏFDQWO\ PRUH likely to report SD compared with those without LUTS/ OAB. These data suggest that the relationship between SD and LUTS/OAB in women should be considered when diagnosing and treating these conditions.
P54 UROTHELIAL TUMOURS: BASIC RESEARCH II Friday, 28 March, 14.00-15.30, Blue Hall 2
876
MSH2 MUTATIONS AND BLADDER CANCER RISK: FAMILY MEMBERS OF HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (HNPCC) PATIENTS WITH MSH2 MUTATIONS ARE AT INCREASED RISK NOT ONLY FOR UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA (TCC) BUT ALSO BLADDER CANCER Skeldon S.1, Semotiuk K.2, Gallinger S.2, Fleshner N., Cotterchio M.2, Jewett M., Zlotta A.4 University of Toronto, Dept. of Urology, Toronto, Canada, 2Mount Sinai Hospital and University of Toronto, Dept. of Gastroenterology, Toronto, Canada, UHN and University of Toronto, Dept. of Urology, Toronto, Canada, 4Mount Sinai Hospital and University of Toronto, Dept. of Urology, Toronto, Canada
1
Introduction & Objectives: We analyzed the risk of bladder cancer and upper tract transitional cell carcinoma (TCC) in patients within families from the Toronto familial colon cancer registry and in particular with MSH2 mutations. Genetic risks for bladder cancer are currently the subject of many investigations. A correlation between hereditary nonpolyposis colorectal cancer and upper tract TCC had been previously described (1) but information about bladder cancer risk in MSH2 mutations within these families is largely unknown. Material & Methods: Cancer data were obtained from the Toronto familial gastrointestinal cancer UHJLVWU\IURP WRLQFOXGLQJSHUVRQVZLWKNQRZQPXWDWLRQV $3&&'+&5$&0/+ MSH6, MYH or FMS2 mutations), among whom 174 had MSH2 mutations. The standardized incidence UDWLRLQ&DQDGD ZHUHXVHGWRPHDVXUHFDQFHUULVNLQRᚎVSULQJVDPRQJIDPLOLHVZLWKSURYHQ06+DQG other mutations according to familial cancer status. Results: :HLGHQWLᚏHGSDWLHQWVZLWKXURWKHOLDOFDQFHUVKDGEODGGHUFDQFHU XSSHU7&& (25%). Thirty-six of these patients had a double primary cancer and 29 (41%) had colon cancer. Among patients with colon cancer, urothelial cancers appeared before colon cancer in 25% of cases. Within the 174 patients in the registry with proven MSH2 mutations, bladder cancer was found in 10 (5.74%) persons but none among the 179 patients with APC, CDH1, CRAC1, MLH1, MSH6, MYH or FMS2 mutations. There were 6 women and 4 men, in contrast with the expected male to female ratio for EODGGHUFDQFHURI LQ&DQDGD 7KLVULVNIRUEODGGHUFDQFHUDPRQJ06+FDUULHUVLVFOHDUO\ increased as compared to the 2.5% and 0.5% lifetime risk among among men and women in Canada, respectively (2). Regarding upper tract TCC among MSH2 carriers, the observed risk was 2.9% (5/174) ZKLFKLVLQOLQHZLWKSUHYLRXVUHSRUWV DERXWWKHVLJQLᚏFDQWO\LQFUHDVHGULVNRIXSSHUWUDFW7&&LQ these populations (1). Conclusions: Siblings of hereditary colorectal cancer patients with MSH2 mutations are at increased risk not only for upper tract TCC as previously demonstrated (which actually can precede the diagnosis of colon cancer) but also of bladder cancer. None of the other genetic markers predisposing to HNPCC was involved in upper tract or bladder cancer TCC. Our study suggests that mutations of mismatch repair proteins may have an important contribution in the development of a subset of TCCs. References 1.Sijmons R.H., Kiemeney L.A., Witjes J.A., Vasen H.F. Urinary tract cancer and hereditary nonpolyposis FRORUHFWDO FDQFHU ULVNV DQG VFUHHQLQJ RSWLRQV - 8URO &DQDGLDQ &DQFHU 6WDWLVWLFV KWWS ZZZQFLFFDQFHUFDYJQLPDJHVSRUWDOFLWB FZB stats_en.pdf
877
878
RESEARCH AND EVALUATION OF NEW MARKERS IN BLADDER CANCER: A PHOSPHOPROTEOMIC STUDY
METHYLATION OF RUNX3 PROMOTER AS A PROMISING PROGNOSTIC MARKER FOR BLADDER TUMOURS
Fiori C.1, Barbero G.2, Giribaldi G.2, Mandili G.2, Destefanis P.1, Ceruti C.1, Bisconti A.1, Carchedi M.T.1, Fontana D.1, Turrini F.2
Kim Y.J.1, Kim T.W.2, Yun S.J.1, Lee H.L.2, Lee S.C.1, Kim W.J.1 1
University of Turin, Dept. of Nefrourologia, Turin, Italy, 2University of Turin, Dept. of Genetica, Biology and Biochimica, Turin, Italy 1
Introduction & Objectives: The most reliable procedure for bladder cancer diagnosis and follow up is cystoscopy with bladder biopsy, this intervention anyway is somewhat invasive DQGH[SDQVLYH7KHLGHQWLᚏFDWLRQRIQHZXULQDU\PDUNHUVFRXOGKDYHDQHQRUPRXVLPSDFW on diagnosis and early treatment of this kind of neoplasm. The discovery of disease markers E\JHQHDQGSURWHLQH[SUHVVLRQSURᚏOLQJWKURXJK'1$PLFURDUUD\DQGSURWHRPLFVSURPLVHV to deliver some solutions to these challenges. However, the activity of protein, that is often UHJXODWHG YLD SRVWWUDQVODWLRQ PRGLᚏFDWLRQV RI ZKLFK SKRVSKRU\ODWLRQ LV RQH RI WKH PRVW prominent, is a more relevant phenotype than its expression during pathogenesis. More than 50% of tyrosine kinases are over expressed or mutated in various human cancers. The aim of this study is to identify new potential bladder cancer protein markers by comparative phospho-proteomic approach for clinical applications. Material & Methods: Bladder cancer samples (5-10 mg) obtained during radical cystectomy or TURB and similar size samples from normal tissues were used. Following extraction proteins were solubilised and separated by 2-DE electrophoresis. Gels obtained were blotted into PVDF membranes and probed with anti-phosphoserine and anti-phosphotyrosine antibody. Afterwards, western-blotting tumoural tissues were compared with normal tissues ,PDJHVDQGGLᚎHUHQWLDOSKRVSKRSURWHLQVZHUHLGHQWLᚏHG,GHQWLᚏFDWLRQVZHUHFDUULHGDIWHU in-gel proteolysis of the electrophoretic spots by MALDI-TOF analysis and peptide mass ᚏQJHUSULQW Results: Tissue samples from patients with histological diagnosis of bladder TCC were analysed. The comparison of serine and tyrosine phosphorylation patterns from healthy DQG FDUFLQRPD WLVVXHV VKRZHG D VLJQLᚏFDQWO\ KLJKHU SKRVSKRU\ODWLRQ VWDWXV LQ FDUFLQRPD WLVVXHV E\VSHFWURPHWULFDQDO\VLVZHLGHQWLᚏHGDERXWWZHQW\SURWHLQVSKRVSKRU\ODWHGRQO\ LQPDOLJQDQWVDPSOHVDQGᚏYHSURWHLQVZLWKXSUHJXODWHGSKRVSKRU\ODWLRQLQFDQFHUWLVVXHV Conclusions: Using minimal amount of tissues from bladder cancer patients and SKRVSKRSURWHRPH DQDO\VLV ZH LGHQWLᚏHG VRPH QHZ SRWHQWLDO SKRVSKRSURWHLQ PDUNHUV 'LDJQRVWLF DQG SURJQRVWLF VLJQLᚏFDQFH RI LGHQWLᚏHG SKRVSKRSURWHLQV ZLOO EH HYDOXDWHG LQ our laboratory in urine samples of healthy and cancer patients. For this purpose we are FUHDWLQJ D SKRVSKRSURWHLQVSHFLᚏF DQWLERG\ FKLS ZKLFK LV RQH RI WKH XOWLPDWH JRDOV IRU routine application of phosphoproteomics in the clinical setting.
Eur Urol Suppl 2008;7(3):290
Chungbuk National University College of Medicine, Dept. of Urology, Cheongju, South Korea, 2Kyung Hee University College of Medicine, Dept. of Urology, Seoul, South Korea Introduction & Objectives: DNA methylation is a key regulator of gene transcription and genomic stability, thus altered DNA methylation is a frequently detected epigenetic change in human cancers. Previously we reported that inactivation of 581; ZKLFK ZDV FDXVHG PDLQO\ E\ HSLJHQHWLF DOWHUDWLRQ ZDV FORVHO\ DVVRFLDWHG ZLWKEODGGHUWXPRXUGHYHORSPHQWVXSHUᚏFLDOUHFXUUHQFHDQGSURJUHVVLRQ7KHDLP RIWKLVVWXG\LVWRHYDOXDWHWKHORQJWHUPIROORZXSUHVXOWVRI581;LQDFWLYDWLRQRQ bladder tumour. Material & Methods: :HXVHGRXUSUHYLRXVO\SXEOLVKHGGDWD &DQFHU5HV IRUPHWK\ODWLRQSDWWHUQVRI581;LQEODGGHUWXPRXUVLQDGGLWLRQWRQHZ GDWDE\PHWK\ODWLRQVSHFLᚏF3&5DQGGLUHFW'1$VHTXHQFLQJ2IWKHVH SDWLHQWV SDWLHQWVIROORZHGSHULRGLFDOO\ZHUHLQFOXGHGLQWKHᚏQDODQDO\VHV0HGLDQIROORZ up period was 49.8 months (1-146). Results: 0HWK\ODWLRQRI581;SURPRWHUZDVIRXQGLQ RI 581; methylation status was not associated with bladder tumour recurrence in long-term IROORZXS 581; PHWK\ODWLRQ ZDV PRUH IUHTXHQWO\ REVHUYHG LQ LQYDVLYH WXPRXUV WKDQ LQ VXSHUᚏFLDO EODGGHU WXPRXUV S 25 &, )XUWKHUPRUH581;PHWK\ODWLRQSDWWHUQVZHUHVLJQLᚏFDQWO\FRUUHODWHGZLWKWXPRXU SURJUHVVLRQ S 25 &, RYHUDOO VXUYLYDO S 25 &, DQG FDQFHUVSHFLᚏF VXUYLYDO S OR: 11.710, 95% CI: 1.510-90.781). Kaplan-Meier estimates also demonstrated VLJQLᚏFDQWGLᚎHUHQFHVLQWXPRXUSURJUHVVLRQ ORJUDQNWHVWS RYHUDOOVXUYLYDO ORJUDQNWHVWS DQGFDQFHUVSHFLᚏFVXUYLYDO ORJUDQNWHVWS E\WKH 581;PHWK\ODWLRQVWDWXV Conclusions: 7KHVH UHVXOWV VWURQJO\ VXJJHVW WKDW LQDFWLYDWLRQ RI 581; GXH WR SURPRWHUPHWK\ODWLRQPLJKWEHDVLJQLᚏFDQWULVNIDFWRUIRULQYDVLYHEODGGHUWXPRXU SURJUHVVLRQRYHUDOOVXUYLYDODQGFDQFHUVSHFLᚏFVXUYLYDO581;PHWK\ODWLRQPD\ be used as a promising marker for assessing prognosis of human bladder tumours.