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144 UNILATERAL POSITIVE PROSTATE BIOPSY PREDICTS MORE FAVORABLE PATHOLOGIC AND ONCOLOGIC OUTCOMES IN SELECTION OF CANDIDATES FOR FOCAL THERAPY
Vol. 183, No. 4, Supplement, Sunday, May 30, 2010
pendent on age (p⫽0.86), number of biopsies (p⫽0.47), BMI (p⫽0.33), and initial PSA value (p⫽0.21). There was a trend that the number of men with a Gleason Score upgrade was statistically lower in men with a prostate volume ⬎35ml compared to men with a prostate volume ⬍35ml (p⫽0.05). Upstaging was statistically not dependent on age (p⫽0.09), the BMI (p⫽0.10), prostate volume (p⫽0.82), and the PSA value (p⫽0.67), but the number of biopsies (p⫽0.01) CONCLUSIONS: Patients who are diagnosed with low risk unilateral prostate cancer using common diagnostic methods are at high risk of harboring more aggressive and advanced PCa. This should be taken into account when considering patients as candidates for active surveillance or hemiablative therapy. Source of Funding: None
THE JOURNAL OF UROLOGY姞
e59
Stem Cell Research Podium 8 Sunday, May 30, 2010
8:00 AM-10:00 AM
145 PAX2 OVEREXPRESSION IN EMBRYOID BODIES INDUCES UPREGULATION OF INTEGRIN ␣8 AND AQUAPORIN-1 INVOLVED IN KIDNEY DEVELOPMENT Akihiro Nakane*, Nagoya, Japan; Ryuichi Nishinakamura, Kumamoto, Japan; Kentaro Mizuno, Yoshiyuki Kojima, Tetsuji Maruyama, Yutaro Hayashi, Kenjiro Kohri, Nagoya, Japan
144 UNILATERAL POSITIVE PROSTATE BIOPSY PREDICTS MORE FAVORABLE PATHOLOGIC AND ONCOLOGIC OUTCOMES IN SELECTION OF CANDIDATES FOR FOCAL THERAPY Julia B Finkelstein*, Douglas S Berkman, Herbert Lepor, Samir S Taneja, New York, NY INTRODUCTION AND OBJECTIVES: In the era of increasing detection of low-risk prostate cancer, focal therapy is emerging as an alternative to traditional treatments. A critical issue remains appropriate candidate selection. We previously demonstrated that men with unilateral cancer at surgery have more favorable pathologic features and oncologic outcomes than men with bilateral cancer. In this study we attempted to determine if men with unilateral cancer on biopsy have more favorable oncologic outcomes than men with bilateral positive biopsies, thereby allowing selection of a lower risk cohort appropriate for focal therapy. METHODS: We reviewed the charts of 1,201 patients who underwent radical prostatectomy from 1996 through 2006. Men with a unilateral positive biopsy (n⫽818) were compared to those with bilateral positive biopsies (n⫽383) with respect to clinical and pathologic features and oncologic outcomes. Biochemical failure was defined as any PSA level greater than 0.1. We further identified a low-risk group (n⫽472) with unilateral positive biopsy, Gleason score 6, preoperative PSA less than 10 ng/ml and normal digital rectal exam. RESULTS: Age and preoperative PSA were similar between the two groups. Patients with unilateral positive biopsy were more likely to have Gleason score 6 than men with bilateral positive biopsy (72% vs 62%, p⫽0.001). Men with unilateral positive biopsies were found to have lower rates of pathologic T3 disease (p⫽0.001), positive surgical margins (p⫽0.001), smaller tumor volume (p⫽0.001) and biochemical failure (p⫽0.008). In a low-risk unilateral cohort, these differences were more pronounced, with positive surgical margins in 5.3% vs 13.2% (p⬍0.001), pathologic T3 disease in 10.8% vs. 26.0% (p⬍0.001) and biochemical failure in 10.5% vs 23.5% (p⬍0.001). In addition, the time to failure in low-risk patients was nearly 1 year (37.5 months vs 26.1 months, p⫽0.003) longer than high-risk patients. When low risk unilateral and bilateral men were compared, adverse pathologic outcomes did not differ. CONCLUSIONS: Although a small portion of men with clinically low-risk unilateral disease on biopsy are found to have adverse pathologic findings at prostatectomy, the majority have organ-confined, favorable risk disease with low risk of recurrence suggesting they may be appropriate candidates for focal therapy strategies. Because bilateral low risk patients had similar outcomes to a low-risk unilateral cohort, they may also be considered for focal therapies depending on the adequacy of mapping techniques. Source of Funding: None
INTRODUCTION AND OBJECTIVES: Transcription factor Pax2 is essential for kidney development in mice, and overexpression of Pax2 in chick embryos leads to ectopic formation of nephric structures. We have generated embryonic stem (ES) cell lines that repress Pax2 expression in a tetracycline-dependent manner and examined their differentiation potential by embryoid body (EB) formation. METHODS: MGZRTcH2 cells, in which gene expression can be controlled by the Tet-off system, were maintained on 0.1% gelatincoated tissue culture plates in Glasgow minimal essential medium, 10% fetal bovine serum, and 103 units/ml mouse leukemia inhibitory factor at 37°C with 5% CO2. MGZRTcH2 cells were electroporated with the Pax2-containing exchange vector. Eight days after electroporation, Pax2-recombinant clones were picked up and recombination was confirmed by Southern blot analysis. ES cells were cultured in the same medium without LIF to induce EB formation by the hanging drop culture method. EBs were analyzed by reverse transcription-PCR and immunocytochemistry. RESULTS: RT-PCR analysis was performed in the parental ES cell line, EBs and clones containing Tet-inducible Pax2. In the presence of Tet (Tet⫹), gene expression patterns were similar to those in parental cells. In the absence of tetracycline, aquaporin-1 (Aqp1) and integrin ␣8 were upregulated when cells were induced to form EBs. EBs derived from these cell lines expressed Pax2 and subsequently integrin f¿8 and Aqp1, both of which are possibly involved in kidney development. We further examined expression changes at the protein level. EBs from ES clones containing Tet-inducible Pax2 were cultured with or without tetracycline, and stained with anti-AQP1 and anti-Pax2 antibodies. Pax2 protein was detected only in the absence of Tet. AQP1 protein was also upregulated in the absence of Tet. Considering the slow induction kinetics, our data suggest that Pax2 and additional factors induced in EBs synergistically regulate the two targets. CONCLUSIONS: ES cell lines with inducible Pax2 expression will also be useful for dissecting genetic cascades functioning in the development of various organs, including the kidney.
Source of Funding: None
pendent on age (p⫽0.86), number of biopsies (p⫽0.47), BMI (p⫽0.33), and initial PSA value (p⫽0.21). There was a trend that the number of men with a Gleason Score upgrade was statistically lower in men with a prostate volume ⬎35ml compared to men with a prostate volume ⬍35ml (p⫽0.05). Upstaging was statistically not dependent on age (p⫽0.09), the BMI (p⫽0.10), prostate volume (p⫽0.82), and the PSA value (p⫽0.67), but the number of biopsies (p⫽0.01) CONCLUSIONS: Patients who are diagnosed with low risk unilateral prostate cancer using common diagnostic methods are at high risk of harboring more aggressive and advanced PCa. This should be taken into account when considering patients as candidates for active surveillance or hemiablative therapy. Source of Funding: None
THE JOURNAL OF UROLOGY姞
e59
Stem Cell Research Podium 8 Sunday, May 30, 2010
8:00 AM-10:00 AM
145 PAX2 OVEREXPRESSION IN EMBRYOID BODIES INDUCES UPREGULATION OF INTEGRIN ␣8 AND AQUAPORIN-1 INVOLVED IN KIDNEY DEVELOPMENT Akihiro Nakane*, Nagoya, Japan; Ryuichi Nishinakamura, Kumamoto, Japan; Kentaro Mizuno, Yoshiyuki Kojima, Tetsuji Maruyama, Yutaro Hayashi, Kenjiro Kohri, Nagoya, Japan
144 UNILATERAL POSITIVE PROSTATE BIOPSY PREDICTS MORE FAVORABLE PATHOLOGIC AND ONCOLOGIC OUTCOMES IN SELECTION OF CANDIDATES FOR FOCAL THERAPY Julia B Finkelstein*, Douglas S Berkman, Herbert Lepor, Samir S Taneja, New York, NY INTRODUCTION AND OBJECTIVES: In the era of increasing detection of low-risk prostate cancer, focal therapy is emerging as an alternative to traditional treatments. A critical issue remains appropriate candidate selection. We previously demonstrated that men with unilateral cancer at surgery have more favorable pathologic features and oncologic outcomes than men with bilateral cancer. In this study we attempted to determine if men with unilateral cancer on biopsy have more favorable oncologic outcomes than men with bilateral positive biopsies, thereby allowing selection of a lower risk cohort appropriate for focal therapy. METHODS: We reviewed the charts of 1,201 patients who underwent radical prostatectomy from 1996 through 2006. Men with a unilateral positive biopsy (n⫽818) were compared to those with bilateral positive biopsies (n⫽383) with respect to clinical and pathologic features and oncologic outcomes. Biochemical failure was defined as any PSA level greater than 0.1. We further identified a low-risk group (n⫽472) with unilateral positive biopsy, Gleason score 6, preoperative PSA less than 10 ng/ml and normal digital rectal exam. RESULTS: Age and preoperative PSA were similar between the two groups. Patients with unilateral positive biopsy were more likely to have Gleason score 6 than men with bilateral positive biopsy (72% vs 62%, p⫽0.001). Men with unilateral positive biopsies were found to have lower rates of pathologic T3 disease (p⫽0.001), positive surgical margins (p⫽0.001), smaller tumor volume (p⫽0.001) and biochemical failure (p⫽0.008). In a low-risk unilateral cohort, these differences were more pronounced, with positive surgical margins in 5.3% vs 13.2% (p⬍0.001), pathologic T3 disease in 10.8% vs. 26.0% (p⬍0.001) and biochemical failure in 10.5% vs 23.5% (p⬍0.001). In addition, the time to failure in low-risk patients was nearly 1 year (37.5 months vs 26.1 months, p⫽0.003) longer than high-risk patients. When low risk unilateral and bilateral men were compared, adverse pathologic outcomes did not differ. CONCLUSIONS: Although a small portion of men with clinically low-risk unilateral disease on biopsy are found to have adverse pathologic findings at prostatectomy, the majority have organ-confined, favorable risk disease with low risk of recurrence suggesting they may be appropriate candidates for focal therapy strategies. Because bilateral low risk patients had similar outcomes to a low-risk unilateral cohort, they may also be considered for focal therapies depending on the adequacy of mapping techniques. Source of Funding: None
INTRODUCTION AND OBJECTIVES: Transcription factor Pax2 is essential for kidney development in mice, and overexpression of Pax2 in chick embryos leads to ectopic formation of nephric structures. We have generated embryonic stem (ES) cell lines that repress Pax2 expression in a tetracycline-dependent manner and examined their differentiation potential by embryoid body (EB) formation. METHODS: MGZRTcH2 cells, in which gene expression can be controlled by the Tet-off system, were maintained on 0.1% gelatincoated tissue culture plates in Glasgow minimal essential medium, 10% fetal bovine serum, and 103 units/ml mouse leukemia inhibitory factor at 37°C with 5% CO2. MGZRTcH2 cells were electroporated with the Pax2-containing exchange vector. Eight days after electroporation, Pax2-recombinant clones were picked up and recombination was confirmed by Southern blot analysis. ES cells were cultured in the same medium without LIF to induce EB formation by the hanging drop culture method. EBs were analyzed by reverse transcription-PCR and immunocytochemistry. RESULTS: RT-PCR analysis was performed in the parental ES cell line, EBs and clones containing Tet-inducible Pax2. In the presence of Tet (Tet⫹), gene expression patterns were similar to those in parental cells. In the absence of tetracycline, aquaporin-1 (Aqp1) and integrin ␣8 were upregulated when cells were induced to form EBs. EBs derived from these cell lines expressed Pax2 and subsequently integrin f¿8 and Aqp1, both of which are possibly involved in kidney development. We further examined expression changes at the protein level. EBs from ES clones containing Tet-inducible Pax2 were cultured with or without tetracycline, and stained with anti-AQP1 and anti-Pax2 antibodies. Pax2 protein was detected only in the absence of Tet. AQP1 protein was also upregulated in the absence of Tet. Considering the slow induction kinetics, our data suggest that Pax2 and additional factors induced in EBs synergistically regulate the two targets. CONCLUSIONS: ES cell lines with inducible Pax2 expression will also be useful for dissecting genetic cascades functioning in the development of various organs, including the kidney.
Source of Funding: None