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THE PREDICTIVE VALUE FOR PROSTATE CANCER OF HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA IN A SET OF CORE BIOPSIES
617
618
PATHOLOGIC CHARACTERISTICS OF CANCER DIAGNOSED DURING THE FOLLOW-UP OF PATIENTS WITH ISOLATED HGPIN ON PREVIOUS BIOPSY
THE PREDICTIVE VALUE FOR PROSTATE CANCER OF HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA IN A SET OF CORE BIOPSIES
Godoy G., Marien T., Kumar A., Huang G., Tareen B., Taneja S.S.
Oxley J.D.1, Gillatt J.2, Cottrell D.2, Cottrell A.2
New York University School of Medicine, Dept. of Urology, New York, United States of America Introduction & Objectives: Men with isolated HGPIN on prostate biopsy have an increased long-term risk of prostate cancer. We have routinely followed these men with empiric delayed interval biopsy. We evaluated the pathology of those PHQGLDJQRVHGZLWKFDQFHULQORQJWHUPIROORZXSLQRUGHUWRGHWHUPLQHWKHFOLQLFDOVLJQLᚏFDQFHRIFDQFHUVGLDJQRVHG in men with isolated HGPIN. Material & Methods: The charts of all patients who underwent prostate biopsy at our institution between 1996 and 2007 ZHUHUHYLHZHGPHQIXOᚏOOHGLQFOXVLRQFULWHULDLQFOXGLQJ LVRODWHG+*3,1RQLQLWLDOH[WHQGHGSURVWDWHELRSV\RIDW OHDVWFRUHVDQG DWOHDVWGHOD\HGLQWHUYDOELRSV\ ',%[ 7KH',%[ZDVW\SLFDOO\SHUIRUPHGZLWKLQ\HDUVRI initial biopsy (as per our internal protocol) in men with stable PSA, or at the urologist’s discretion in men with rising PSA. Patients diagnosed with prostate cancer at DIBX1 or DIBx2 were analyzed with respect to time to diagnosis, Gleason score, number of positive cores, location and cancer volume. We also analyzed the pathologic outcomes of men who subsequently underwent radical prostatectomy with respect to pathologic stage, Gleason score, disease volume and margin status. Results: $PRQJSDWLHQWVZLWKDPHDQIROORZXSRIPRQWKV UDQJH PRQWKV ZHIRXQGDQRYHUDOO FDQFHU GHWHFWLRQ UDWH RI 7KH PHDQ WLPH WR FDQFHU GLDJQRVLV ZDV PRQWKV UDQJH PRQWKV 3DWKRORJLF FKDUDFWHULVWLFV DUH GHVFULEHG LQ 7DEOH PHQ KDG *OHDVRQ ุ RQ ELRSV\ $PRQJ WKRVH ZKR KDG FDQFHUGLDJQRVLVRQELRSV\ Q XQGHUZHQWUDGLFDOSURVWDWHFWRP\$OOZHUHS7DQGRQO\KDGSRVLWLYHVXUJLFDO PDUJLQVSDWLHQWVKDG*OHDVRQDQGSDWLHQWVKDG (LJKWSDWLHQWV KDGGLVHDVHYROXPHRIOHVVWKDQ 10%. Table 1: n Mean follow-up time (months) Mean PSA Gleason score median ุ # positive cores 1-2 ุ Location of tumor sextant far lateral transition zone Cancer % on biopsy ื 5-10% ุ
DIBx1 27 29.19 8.65
DIBx2 11
6
7 6/11 (54.5)
10 1
6 1
14 7 2
1 6 1
14 1
7 2 1
Conclusions: &DQFHUVGLDJQRVHGLQORQJWHUPIROORZXSRILVRODWHG+*3,1DUHFOLQLFDOO\VLJQLᚏFDQWLQPRVWFDVHV RIPHQKDYHKLJKJUDGHGLVHDVH7KHXVHRIHPSLULFGHOD\HGLQWHUYDOELRSVLHVDWD\HDULQWHUYDOLQIROORZXSRI+*3,1 LGHQWLᚏHGFOLQLFDOO\VLJQLᚏFDQWEXWORFDOO\FRQᚏQHGGLVHDVHLQDOOFDVHVWRGDWH+*3,1LVUHSUHVHQWDWLYHRIDQLQFUHDVHG long-term risk of prostate cancer and requires rigorous follow-up, inclusive of empiric delayed interval biopsy.
1 Southmead Hospital, Dept. of Histopathology, Bristol, United Kingdom, 2Southmead Hospital, Dept. of Urology, Bristol, United Kingdom
Introduction & Objectives: High grade prostatic intraepithelial neoplasia (PIN) is thought WREHWKHPDLQSUHFXUVRUOHVLRQRISURVWDWHFDQFHU 3&D 7KHᚏQGLQJRI+*3,1LQDQHHGOH FRUHELRSV\LVDVLJQLᚏFDQWULVNIDFWRUIRU3&DEXWRYHUWKHODVWGHFDGHWKHSUHGLFWLYHYDOXHRI ᚏQGLQJ3&DLQDVXEVHTXHQWFRUHELRSV\KDVGHFUHDVHG7KLVVWXG\ORRNHGDWWKHSUHGLFWLYH value in a UK institution and compared the rate of PCa following a set of cores with HGPIN to that of a set of cores without. Material & Methods: 7KHSDWKRORJ\ᚏOHVZHUHH[DPLQHGRYHUDᚏYH\HDUSHULRG LQFOXVLYH3DWLHQWVKDYLQJPRUHWKDQRQHVHWRIELRSVLHVLQWKLVSHULRGZHUHLGHQWLᚏHG7KH PSA value at the time of biopsy was also recorded. All patients had a minimum of 10 cores per set of biopsies. Results: 2YHUWKHᚏYH\HDUSHULRGWKHUHZHUHVHWVRIFRUHELRSVLHVDQGRIWKHVH ZHUH QHJDWLYH FRQWDLQHG 3&D KDG +*3,1 DQG KDG$6$37KHVHELRSVLHVRULJLQDWHGIURP SDWLHQWV KDGDVLQJOHVHWRI biopsies, 429(15%) had at least one set of repeat biopsies. 47(19%) of the 254 patients ZLWKDQHJDWLYHELRSV\KDG3&DLQDVXEVHTXHQWELRSV\ RIWKHSDWLHQWVZLWK +*3,1KDG3&DLQDVXEVHTXHQWELRSV\ RIWKHSDWLHQWVZLWK$6$3KDG3&DLQ a subsequent biopsy. The mean serum PSA of the 47 patients with a positive set of cores IROORZLQJDQHJDWLYHELRSV\ZDV FRPSDUHGZLWKRIWKHSDWLHQWVZLWK+*3,1ZKR KDG3&DLQDVXEVHTXHQWVHWRIFRUHV,IWKHVHUHVXOWVDUHVWUDWLᚏHGRQWKHEDVLVRI36$YDOXH of above or below 20 then the following results were found: Initial biopsy negative and PSA WKHQ RIVXEVHTXHQWELRSVLHVVKRZHG3&D,QLWLDOELRSV\+*3,1DQG36$ WKHQ RIVXEVHTXHQWELRSVLHVVKRZHG3&D,QLWLDOELRSV\$6$3DQG36$ WKHQ RIVXEVHTXHQWELRSVLHVVKRZHG3&D2ILPSRUWDQWLQWHUHVW ,QLWLDOELRSV\QHJDWLYH and PSA <20 then 12 (66%) of subsequent biopsies showed PCa. Conclusions: Recent studies have suggested that the predictive value of HGPIN is little PRUHWKDQWKDWRIDQHJDWLYHUHVXOW7KLVVWXG\KDVVKRZQWKDW+*3,1LVVWLOODVLJQLᚏFDQW marker of risk of prostate cancer in subsequent set of core biopsies. If PSA is also taken into account then if a patient has PSA of less than 20 then he is twice as likely to have PCa in a VXEVHTXHQWVHWRIELRSVLHVLIKLVᚏUVWVHWKDV+*3,1WKDQLIWKH\ZHUHQHJDWLYH,IWKHᚏUVWVHW of core is negative and his PSA is >20 then there is a 66% of PCa in subsequent cores.
619 WHICH GLEASON SCORE SHOULD BE APPLIED, GLOBAL OR HIGHEST GLEASON SCORE? GRADE CONCORDANCE BETWEEN EXTENDED BIOPSY AND PROSTATECTOMY ACCORDING TO MODIFIED GLEASON GRADING SYSTEM Numao N.1, Kawakami K.1, Sakura S.1, Yonese Y.2, Fukui F.2, Ishikawa I., Kihara K.1
620 MOLECULAR TRANSCRIPT PROFILING IN FORMALIN FIXED PARAFFIN EMBEDDED DIAGNOSTIC PROSTATE CANCER NEEDLE BIOPSIES Rogerson L.1, Darby S.1, Jabbar T.1, Robson C.1, O’toole K.1, Leung H.2, Mathers M., Sahadevan K.4, Gnanapragasam V.1 1
Tokyo Medical and Dental University, Dept. of Urology, Tokyo, Japan, 2Cancer institute, Japanese Foundation for Cancer Research, Dept. of Urology, Tokyo, Japan, Cancer institute, Japanese Foundation for Cancer Research, Dept. of Pathology, Tokyo, Japan 1
Introduction & Objectives: As extended biopsy has become widespread, patients with PXOWLSOHSRVLWLYHFDQFHUFRUHVZLWKGLᚎHUHQW*OHDVRQVFRUH *6 LVLQFUHDVLQJ,WLVFRQWURYHUVLDO which GS should be applied to the GS of the entire case, global GS (GGS) or highest GS (HGS). We studied which GS is adequate to predict radical prostatectomy GS (RPGS). Material & Methods: We obtained the clinical data and the pathological reports of 151 FRQVHFXWLYHSDWLHQWVZLWKFOLQLFDOO\RUJDQFRQᚏQHGSURVWDWHFDQFHUGLDJQRVHGE\WKHWKUHH GLPHQVLRQDO FRUH ELRSV\ '3%[ DQG WUHDWHG ZLWK UDGLFDO SURVWDWHFWRP\ ZLWKRXW QHRDGMXYDQW WKHUDS\ 7KH '3%[ LV D FRPELQHG ELRSV\ VFKHPH RI WUDQVUHFWDO FRUH biopsy (TR12PBx) and transperineal 14-core biopsy. GS was reviewed according to the 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading. We assigned GS for all positive cores and determined GGS and HGS. GGS was GHᚏQHGDVWKHRYHUDOO*6DYHUDJLQJDOOLQYROYHGQHHGOHELRSVLHVWRJHWKHULIWKH\ZHUHRQH ORQJSRVLWLYHFRUH+*6ZDVGHᚏQHGDVWKHKLJKHVW*6DPRQJHDFKSRVLWLYHFRUH**6DQG +*6ZHUHFODVVLᚏHGLQWRIROORZLQJJURXSVRUOHVVRUPRUH:HLQYHVWLJDWHG discordance rate between GGS and HGS, and which GS better correlated with RPGS when GGS and HGS were discordant. We also investigated in patients with cancers detected by 753%[WKHVXEVHWRIWKH'ELRSV\ Results: 'LVFRUGDQFHUDWHEHWZHHQ**6DQG+*6ZHUH DQG LQ '3%[DQG753%[UHVSHFWLYHO\:KHQ**6DQG+*6ZHUHGLVFRUGDQWFRQFRUGDQFH rates between GGS/HGS and RPGS were 50% (25/51:GGS) and 18% (9/51:HGS) in '3%[VLPLODUO\FRQFRUGDQFHUDWHVEHWZHHQ**6+*6DQG53*6ZHUH **6 DQG +*6 LQ753%[7KXV**6ZDVDVLJQLᚏFDQWO\EHWWHUSUHGLFWRURI53*6 FRPSDUHGWR+*6LQERWK'3%[DQG753%[,I+*6ZRXOGDSSO\WR*6RIWKHHQWLUH FDVH DQG ZRXOGEHRYHUJUDGLQJ +*6!35* LQ'3%[DQG TR12PBx, respectively. Conclusions: When GGS and HGS were discordant in extended biopsy, GGS was correlated ZLWK53*6EHWWHUWKDQ+*6DFFRUGLQJWRWKH,683PRGLᚏHG*OHDVRQV\VWHP5LVNRI over grading should be considered when HG is applied.
Northern Institute for Cancer Research, Dept. of Surgical Oncology, Newcastle upon Tyne, United Kingdom, 2Beatson Institute, Dept. of Surgical Oncology, Glasgow, United Kingdom, Royal Victoria ,QᚏUPDU\ 'HSW RI 3DWKRORJ\ 1HZFDVWOH 8QLWHG .LQJGRP 46XQGHUODQG 5R\DO ,QᚏUPDU\ 'HSW RI Urology, Sunderland, United Kingdom Introduction & Objectives: The clinical value of a prognostic tissue molecular marker is at the point of diagnosis. In prostate cancer however, tissue heterogeneity, small tumour volumes as well as formalin ᚏ[DWLRQKDYHVRIDUSURKLELWHGWUDQVFULSWDQGPLFURDUUD\SURᚏOLQJLQGLDJQRVWLFWUDQVUHFWDOXOWUDVRXQG guided needle biopsies. We investigated the use of Laser Capture Micro dissection (LCM) to acquire PDOLJQDQWDQGEHQLJQJODQGXODUHSLWKHOLXPLQGLDJQRVWLFDUFKLYDO)RUPDOLQ)L[HG3DUDᚑQ(PEHGGHG (FFPE) prostate biopsies. Material & Methods: LCM was used to micro dissect epithelial and stromal tissue in archival FFPE prostate needle biopsies premarked by a uro-pathologist. An initial pilot cohort of biopsies from 5 men were studied followed by an extended study with separate biopsies from 29 men. Optimised RNA extraction, reverse transcription and real time PCR (QPCR) protocols were developed and used to GHWHFW WUDQVFULSW H[SUHVVLRQ LQ WKLV WLVVXH 7KH HᚎHFWV RI 51$ GHJUDGDWLRQ RQ WUDQVFULSW H[SUHVVLRQ ZHUH LQYHVWLJDWHG XVLQJ '8 DQG 3& FHOO 51$ GHJUDGHG E\ KHDW WUHDWPHQW IRU LQFUHDVLQJ WLPH OHQJWKV 7KH HᚎHFWV RI IRUPDOLQ ᚏ[DWLRQ DQG SDUDᚑQ VWRUDJH ZHUH DOVR VWXGLHG XVLQJ DQ DUFKLYDO xenograft tumour. Results: RNA was successfully extracted from micro dissected malignant and benign epithelium as ZHOODVVWRPDLQDSLORWFRKRUWRIELRSVLHV Q 3UHDQGSRVWGLVVHFWLRQLPDJHVZHUHWDNHQWRFRQᚏUP the accuracy of the dissection. cDNA produced was used to detect expression of a number of transcripts LQFOXGLQJ*$3'+53/36$9LPHQWLQ,GDQG(=+))3(UHVXOWVLQ51$GHJUDGDWLRQZKLFKFDQ DᚎHFWWUDQVFULSWTXDQWLᚏFDWLRQ7RDVVHVVDPHWKRGWRFRUUHFWIRUWKLVZHXVHGGHJUDGHGFHOOOLQH51$ and matched FFPE and frozen tumours from a xenograft model (CWR22). In these we observed a disparity in transcript gene expression between RNA degraded samples and intact controls. In both models however normalisation of transcript quantity with a housekeeping gene restored expression LQ 51$ GHJUDGHG VDPSOHV WR ZLWKLQ D IROG GLᚎHUHQFH RI OHYHOV VHHQ LQ FRQWURO VDPSOHV 8VLQJ these methods we investigated an extended cohort of biopsies (n=29) to test application in detecting GLᚎHUHQFHVEHWZHHQPDOLJQDQWDQGEHQLJQWLVVXH,QWKHVHZHTXDQWLᚏHGH[SUHVVLRQRIWKH(=+DQG ,GWUDQVFULSWVZKLFKKDYHEHHQLPSOLFDWHGLQSURVWDWHFDQFHU2XUUHVXOWVFRQᚏUPHGGLᚎHUHQWSDWWHUQV of expression in malignant and benign tissue consistent with the reported trends in the literature. Conclusions: :H GHVFULEH KHUH WR RXU NQRZOHGJH WKH ᚏUVW XVH RI DUFKLYDO GLDJQRVWLF ELRSVLHV IRU molecular transcript studies in prostate cancer. Using currently available technology we demonstrate DSSOLFDWLRQLQLVRODWLQJPDOLJQDQWHSLWKHOLXPDQGSURᚏOLQJJHQHWUDQVFULSWH[SUHVVLRQ7KLVSUHOLPLQDU\ study supports the concept of molecular prognostic studies in tissue acquired at the point of diagnosis in prostate cancer.
Eur Urol Suppl 2008;7(3):225
618
PATHOLOGIC CHARACTERISTICS OF CANCER DIAGNOSED DURING THE FOLLOW-UP OF PATIENTS WITH ISOLATED HGPIN ON PREVIOUS BIOPSY
THE PREDICTIVE VALUE FOR PROSTATE CANCER OF HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA IN A SET OF CORE BIOPSIES
Godoy G., Marien T., Kumar A., Huang G., Tareen B., Taneja S.S.
Oxley J.D.1, Gillatt J.2, Cottrell D.2, Cottrell A.2
New York University School of Medicine, Dept. of Urology, New York, United States of America Introduction & Objectives: Men with isolated HGPIN on prostate biopsy have an increased long-term risk of prostate cancer. We have routinely followed these men with empiric delayed interval biopsy. We evaluated the pathology of those PHQGLDJQRVHGZLWKFDQFHULQORQJWHUPIROORZXSLQRUGHUWRGHWHUPLQHWKHFOLQLFDOVLJQLᚏFDQFHRIFDQFHUVGLDJQRVHG in men with isolated HGPIN. Material & Methods: The charts of all patients who underwent prostate biopsy at our institution between 1996 and 2007 ZHUHUHYLHZHGPHQIXOᚏOOHGLQFOXVLRQFULWHULDLQFOXGLQJ LVRODWHG+*3,1RQLQLWLDOH[WHQGHGSURVWDWHELRSV\RIDW OHDVWFRUHVDQG DWOHDVWGHOD\HGLQWHUYDOELRSV\ ',%[ 7KH',%[ZDVW\SLFDOO\SHUIRUPHGZLWKLQ\HDUVRI initial biopsy (as per our internal protocol) in men with stable PSA, or at the urologist’s discretion in men with rising PSA. Patients diagnosed with prostate cancer at DIBX1 or DIBx2 were analyzed with respect to time to diagnosis, Gleason score, number of positive cores, location and cancer volume. We also analyzed the pathologic outcomes of men who subsequently underwent radical prostatectomy with respect to pathologic stage, Gleason score, disease volume and margin status. Results: $PRQJSDWLHQWVZLWKDPHDQIROORZXSRIPRQWKV UDQJH PRQWKV ZHIRXQGDQRYHUDOO FDQFHU GHWHFWLRQ UDWH RI 7KH PHDQ WLPH WR FDQFHU GLDJQRVLV ZDV PRQWKV UDQJH PRQWKV 3DWKRORJLF FKDUDFWHULVWLFV DUH GHVFULEHG LQ 7DEOH PHQ KDG *OHDVRQ ุ RQ ELRSV\ $PRQJ WKRVH ZKR KDG FDQFHUGLDJQRVLVRQELRSV\ Q XQGHUZHQWUDGLFDOSURVWDWHFWRP\$OOZHUHS7DQGRQO\KDGSRVLWLYHVXUJLFDO PDUJLQVSDWLHQWVKDG*OHDVRQDQGSDWLHQWVKDG (LJKWSDWLHQWV KDGGLVHDVHYROXPHRIOHVVWKDQ 10%. Table 1: n Mean follow-up time (months) Mean PSA Gleason score median ุ # positive cores 1-2 ุ Location of tumor sextant far lateral transition zone Cancer % on biopsy ื 5-10% ุ
DIBx1 27 29.19 8.65
DIBx2 11
6
7 6/11 (54.5)
10 1
6 1
14 7 2
1 6 1
14 1
7 2 1
Conclusions: &DQFHUVGLDJQRVHGLQORQJWHUPIROORZXSRILVRODWHG+*3,1DUHFOLQLFDOO\VLJQLᚏFDQWLQPRVWFDVHV RIPHQKDYHKLJKJUDGHGLVHDVH7KHXVHRIHPSLULFGHOD\HGLQWHUYDOELRSVLHVDWD\HDULQWHUYDOLQIROORZXSRI+*3,1 LGHQWLᚏHGFOLQLFDOO\VLJQLᚏFDQWEXWORFDOO\FRQᚏQHGGLVHDVHLQDOOFDVHVWRGDWH+*3,1LVUHSUHVHQWDWLYHRIDQLQFUHDVHG long-term risk of prostate cancer and requires rigorous follow-up, inclusive of empiric delayed interval biopsy.
1 Southmead Hospital, Dept. of Histopathology, Bristol, United Kingdom, 2Southmead Hospital, Dept. of Urology, Bristol, United Kingdom
Introduction & Objectives: High grade prostatic intraepithelial neoplasia (PIN) is thought WREHWKHPDLQSUHFXUVRUOHVLRQRISURVWDWHFDQFHU 3&D 7KHᚏQGLQJRI+*3,1LQDQHHGOH FRUHELRSV\LVDVLJQLᚏFDQWULVNIDFWRUIRU3&DEXWRYHUWKHODVWGHFDGHWKHSUHGLFWLYHYDOXHRI ᚏQGLQJ3&DLQDVXEVHTXHQWFRUHELRSV\KDVGHFUHDVHG7KLVVWXG\ORRNHGDWWKHSUHGLFWLYH value in a UK institution and compared the rate of PCa following a set of cores with HGPIN to that of a set of cores without. Material & Methods: 7KHSDWKRORJ\ᚏOHVZHUHH[DPLQHGRYHUDᚏYH\HDUSHULRG LQFOXVLYH3DWLHQWVKDYLQJPRUHWKDQRQHVHWRIELRSVLHVLQWKLVSHULRGZHUHLGHQWLᚏHG7KH PSA value at the time of biopsy was also recorded. All patients had a minimum of 10 cores per set of biopsies. Results: 2YHUWKHᚏYH\HDUSHULRGWKHUHZHUHVHWVRIFRUHELRSVLHVDQGRIWKHVH ZHUH QHJDWLYH FRQWDLQHG 3&D KDG +*3,1 DQG KDG$6$37KHVHELRSVLHVRULJLQDWHGIURP SDWLHQWV KDGDVLQJOHVHWRI biopsies, 429(15%) had at least one set of repeat biopsies. 47(19%) of the 254 patients ZLWKDQHJDWLYHELRSV\KDG3&DLQDVXEVHTXHQWELRSV\ RIWKHSDWLHQWVZLWK +*3,1KDG3&DLQDVXEVHTXHQWELRSV\ RIWKHSDWLHQWVZLWK$6$3KDG3&DLQ a subsequent biopsy. The mean serum PSA of the 47 patients with a positive set of cores IROORZLQJDQHJDWLYHELRSV\ZDV FRPSDUHGZLWKRIWKHSDWLHQWVZLWK+*3,1ZKR KDG3&DLQDVXEVHTXHQWVHWRIFRUHV,IWKHVHUHVXOWVDUHVWUDWLᚏHGRQWKHEDVLVRI36$YDOXH of above or below 20 then the following results were found: Initial biopsy negative and PSA WKHQ RIVXEVHTXHQWELRSVLHVVKRZHG3&D,QLWLDOELRSV\+*3,1DQG36$ WKHQ RIVXEVHTXHQWELRSVLHVVKRZHG3&D,QLWLDOELRSV\$6$3DQG36$ WKHQ RIVXEVHTXHQWELRSVLHVVKRZHG3&D2ILPSRUWDQWLQWHUHVW ,QLWLDOELRSV\QHJDWLYH and PSA <20 then 12 (66%) of subsequent biopsies showed PCa. Conclusions: Recent studies have suggested that the predictive value of HGPIN is little PRUHWKDQWKDWRIDQHJDWLYHUHVXOW7KLVVWXG\KDVVKRZQWKDW+*3,1LVVWLOODVLJQLᚏFDQW marker of risk of prostate cancer in subsequent set of core biopsies. If PSA is also taken into account then if a patient has PSA of less than 20 then he is twice as likely to have PCa in a VXEVHTXHQWVHWRIELRSVLHVLIKLVᚏUVWVHWKDV+*3,1WKDQLIWKH\ZHUHQHJDWLYH,IWKHᚏUVWVHW of core is negative and his PSA is >20 then there is a 66% of PCa in subsequent cores.
619 WHICH GLEASON SCORE SHOULD BE APPLIED, GLOBAL OR HIGHEST GLEASON SCORE? GRADE CONCORDANCE BETWEEN EXTENDED BIOPSY AND PROSTATECTOMY ACCORDING TO MODIFIED GLEASON GRADING SYSTEM Numao N.1, Kawakami K.1, Sakura S.1, Yonese Y.2, Fukui F.2, Ishikawa I., Kihara K.1
620 MOLECULAR TRANSCRIPT PROFILING IN FORMALIN FIXED PARAFFIN EMBEDDED DIAGNOSTIC PROSTATE CANCER NEEDLE BIOPSIES Rogerson L.1, Darby S.1, Jabbar T.1, Robson C.1, O’toole K.1, Leung H.2, Mathers M., Sahadevan K.4, Gnanapragasam V.1 1
Tokyo Medical and Dental University, Dept. of Urology, Tokyo, Japan, 2Cancer institute, Japanese Foundation for Cancer Research, Dept. of Urology, Tokyo, Japan, Cancer institute, Japanese Foundation for Cancer Research, Dept. of Pathology, Tokyo, Japan 1
Introduction & Objectives: As extended biopsy has become widespread, patients with PXOWLSOHSRVLWLYHFDQFHUFRUHVZLWKGLᚎHUHQW*OHDVRQVFRUH *6 LVLQFUHDVLQJ,WLVFRQWURYHUVLDO which GS should be applied to the GS of the entire case, global GS (GGS) or highest GS (HGS). We studied which GS is adequate to predict radical prostatectomy GS (RPGS). Material & Methods: We obtained the clinical data and the pathological reports of 151 FRQVHFXWLYHSDWLHQWVZLWKFOLQLFDOO\RUJDQFRQᚏQHGSURVWDWHFDQFHUGLDJQRVHGE\WKHWKUHH GLPHQVLRQDO FRUH ELRSV\ '3%[ DQG WUHDWHG ZLWK UDGLFDO SURVWDWHFWRP\ ZLWKRXW QHRDGMXYDQW WKHUDS\ 7KH '3%[ LV D FRPELQHG ELRSV\ VFKHPH RI WUDQVUHFWDO FRUH biopsy (TR12PBx) and transperineal 14-core biopsy. GS was reviewed according to the 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading. We assigned GS for all positive cores and determined GGS and HGS. GGS was GHᚏQHGDVWKHRYHUDOO*6DYHUDJLQJDOOLQYROYHGQHHGOHELRSVLHVWRJHWKHULIWKH\ZHUHRQH ORQJSRVLWLYHFRUH+*6ZDVGHᚏQHGDVWKHKLJKHVW*6DPRQJHDFKSRVLWLYHFRUH**6DQG +*6ZHUHFODVVLᚏHGLQWRIROORZLQJJURXSVRUOHVVRUPRUH:HLQYHVWLJDWHG discordance rate between GGS and HGS, and which GS better correlated with RPGS when GGS and HGS were discordant. We also investigated in patients with cancers detected by 753%[WKHVXEVHWRIWKH'ELRSV\ Results: 'LVFRUGDQFHUDWHEHWZHHQ**6DQG+*6ZHUH DQG LQ '3%[DQG753%[UHVSHFWLYHO\:KHQ**6DQG+*6ZHUHGLVFRUGDQWFRQFRUGDQFH rates between GGS/HGS and RPGS were 50% (25/51:GGS) and 18% (9/51:HGS) in '3%[VLPLODUO\FRQFRUGDQFHUDWHVEHWZHHQ**6+*6DQG53*6ZHUH **6 DQG +*6 LQ753%[7KXV**6ZDVDVLJQLᚏFDQWO\EHWWHUSUHGLFWRURI53*6 FRPSDUHGWR+*6LQERWK'3%[DQG753%[,I+*6ZRXOGDSSO\WR*6RIWKHHQWLUH FDVH DQG ZRXOGEHRYHUJUDGLQJ +*6!35* LQ'3%[DQG TR12PBx, respectively. Conclusions: When GGS and HGS were discordant in extended biopsy, GGS was correlated ZLWK53*6EHWWHUWKDQ+*6DFFRUGLQJWRWKH,683PRGLᚏHG*OHDVRQV\VWHP5LVNRI over grading should be considered when HG is applied.
Northern Institute for Cancer Research, Dept. of Surgical Oncology, Newcastle upon Tyne, United Kingdom, 2Beatson Institute, Dept. of Surgical Oncology, Glasgow, United Kingdom, Royal Victoria ,QᚏUPDU\ 'HSW RI 3DWKRORJ\ 1HZFDVWOH 8QLWHG .LQJGRP 46XQGHUODQG 5R\DO ,QᚏUPDU\ 'HSW RI Urology, Sunderland, United Kingdom Introduction & Objectives: The clinical value of a prognostic tissue molecular marker is at the point of diagnosis. In prostate cancer however, tissue heterogeneity, small tumour volumes as well as formalin ᚏ[DWLRQKDYHVRIDUSURKLELWHGWUDQVFULSWDQGPLFURDUUD\SURᚏOLQJLQGLDJQRVWLFWUDQVUHFWDOXOWUDVRXQG guided needle biopsies. We investigated the use of Laser Capture Micro dissection (LCM) to acquire PDOLJQDQWDQGEHQLJQJODQGXODUHSLWKHOLXPLQGLDJQRVWLFDUFKLYDO)RUPDOLQ)L[HG3DUDᚑQ(PEHGGHG (FFPE) prostate biopsies. Material & Methods: LCM was used to micro dissect epithelial and stromal tissue in archival FFPE prostate needle biopsies premarked by a uro-pathologist. An initial pilot cohort of biopsies from 5 men were studied followed by an extended study with separate biopsies from 29 men. Optimised RNA extraction, reverse transcription and real time PCR (QPCR) protocols were developed and used to GHWHFW WUDQVFULSW H[SUHVVLRQ LQ WKLV WLVVXH 7KH HᚎHFWV RI 51$ GHJUDGDWLRQ RQ WUDQVFULSW H[SUHVVLRQ ZHUH LQYHVWLJDWHG XVLQJ '8 DQG 3& FHOO 51$ GHJUDGHG E\ KHDW WUHDWPHQW IRU LQFUHDVLQJ WLPH OHQJWKV 7KH HᚎHFWV RI IRUPDOLQ ᚏ[DWLRQ DQG SDUDᚑQ VWRUDJH ZHUH DOVR VWXGLHG XVLQJ DQ DUFKLYDO xenograft tumour. Results: RNA was successfully extracted from micro dissected malignant and benign epithelium as ZHOODVVWRPDLQDSLORWFRKRUWRIELRSVLHV Q 3UHDQGSRVWGLVVHFWLRQLPDJHVZHUHWDNHQWRFRQᚏUP the accuracy of the dissection. cDNA produced was used to detect expression of a number of transcripts LQFOXGLQJ*$3'+53/36$9LPHQWLQ,GDQG(=+))3(UHVXOWVLQ51$GHJUDGDWLRQZKLFKFDQ DᚎHFWWUDQVFULSWTXDQWLᚏFDWLRQ7RDVVHVVDPHWKRGWRFRUUHFWIRUWKLVZHXVHGGHJUDGHGFHOOOLQH51$ and matched FFPE and frozen tumours from a xenograft model (CWR22). In these we observed a disparity in transcript gene expression between RNA degraded samples and intact controls. In both models however normalisation of transcript quantity with a housekeeping gene restored expression LQ 51$ GHJUDGHG VDPSOHV WR ZLWKLQ D IROG GLᚎHUHQFH RI OHYHOV VHHQ LQ FRQWURO VDPSOHV 8VLQJ these methods we investigated an extended cohort of biopsies (n=29) to test application in detecting GLᚎHUHQFHVEHWZHHQPDOLJQDQWDQGEHQLJQWLVVXH,QWKHVHZHTXDQWLᚏHGH[SUHVVLRQRIWKH(=+DQG ,GWUDQVFULSWVZKLFKKDYHEHHQLPSOLFDWHGLQSURVWDWHFDQFHU2XUUHVXOWVFRQᚏUPHGGLᚎHUHQWSDWWHUQV of expression in malignant and benign tissue consistent with the reported trends in the literature. Conclusions: :H GHVFULEH KHUH WR RXU NQRZOHGJH WKH ᚏUVW XVH RI DUFKLYDO GLDJQRVWLF ELRSVLHV IRU molecular transcript studies in prostate cancer. Using currently available technology we demonstrate DSSOLFDWLRQLQLVRODWLQJPDOLJQDQWHSLWKHOLXPDQGSURᚏOLQJJHQHWUDQVFULSWH[SUHVVLRQ7KLVSUHOLPLQDU\ study supports the concept of molecular prognostic studies in tissue acquired at the point of diagnosis in prostate cancer.
Eur Urol Suppl 2008;7(3):225