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123 ENGRAILED-2 (EN2): A HIGHLY SPECIFIC URINARY BIOMARKER FOR THE EARLY DIAGNOSIS OF PROSTATE CANCER
better (p = 0.027) for the RTE guided approach with 51.1% (91 of 178 patients) compared to 39.4% (69 of 175 patients) for GSU. Overall, sensitivity and specificity for predicting PCa were 60.8% and 68.4% for RTE and 15% and 92.3% for GSU, respectively. A trend for increasing sensitivity could be observed from base (34.245%) to apex (60-76.9%) for RTE only. Conclusions: RTE imaging significantly improves the sensitivity of systematic 10core biopsy to detect prostate cancer. Compared to GSU, the imaging information supported by RTE is more capable to predict cancer suspicion.
123
Engrailed-2 (EN2): A highly specific urinary biomarker for the early diagnosis of prostate cancer
Morgan R.M.1, Ismail M.1, Boxall A.1, Bhaat A.1, Hindley R.2, Michael A.1, Langley S.M.3, Zylstra J.1, Pandha H.S.1 1 Postgraduate Medical School, Dept. of Urological Oncology, Guildford, United Kingdom, 2Basingstoke Hospital, Dept. of Urology, Basingstoke, United Kingdom, 3 Royal Surrey Hospital, Dept. of Urology, Guildford, United Kingdom Introduction & Objectives: Despite recent publication of numerous putative biomarkers of prostate cancer (PC)and the development of 'risk models' we are still completely dependent clinically on serum PSA. There is therefore an urgent need for new diagnostic biomarkers and particularly those identifying 'significant cancers' . A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, have to be overcome such as raised levels in non-cancer disorders of the prostate . We have assessed the diagnostic potential of EN2 protein, a homeodomain-containing transcription factor expressed in PC cell lines, prostate cancer tissue and secreted into the urine by PC in men. Materials & Methods: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine (without prior digital rectal examination (DRE)) was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n=82) and controls (n=102). Controls included men with high PSA who were biopsy negative as well as low PSA with no symptoms or family history recruited from a 'well man' health screening program. Results: EN2 expression was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. We evaluated tissue from our clinical cases in our practice and large PC tissue arrays. EN2 is stable in urine for 4 days at room temperature. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results we confirmed independently by evaluation of men with PC and controls from a second academic centre at Cambridge University. Conclusions: This study evaluated a transcription factor secreted by PC as a simple ELISA test without the requirement for DRE. Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. The high sensitivity, specificity and stability of EN2 at room temperature would make this test attractive as a simple screening tool in the community. The lack of requirement for DRE and its stability differentiates it from other tests currently under evaluation. The ELISA test used for EN2 detection can be simply converted to a lateral flow or 'dipstick' format for ease of use potentially in the primary care setting. A larger multicentre study to further evaluate the diagnostic and monitoring potential of EN2 is justified.
124
Tumor configuration of prostate cancer (PCa) influences the sensitivity of [11C]choline positron emission tomography/computed tomography (PET/CT)
Maurer T.1, Souvatzoglou M.2, Weirich G.3, Schwarzenboeck S.2, Schuster T.4, Herrmann K.2, Kübler H.1, Wester H.J.2, Gschwend J.E.1, Schwaiger M.2, Krause B.J.2, Treiber U.1 1 Technical University Munich, Dept. of Urology, Munich, Germany, 2Technical University Munich, Dept. of Nuclear Medicine, Munich, Germany, 3Technical University Munich, Institute of Pathology, Munich, Germany, 4Technical University Munich, Institute of Medical Statistics and Epidemiology, Munich, Germany Introduction & Objectives: The purpose of this prospective study was to evaluate the diagnostic efficacy of [11C] choline-PET/CT in differentiating PCa from highgrade prostatic intraepithelial neoplasia (HGPIN), benign prostate hyperplasia (BPH) and prostatitis and for detecting and localising PCa in the prostate with respect to tumor configuration in the histologic specimen. Materials & Methods: 43 patients with biopsy proven PCa underwent radical prostatectomy after [11C] choline PET/CT. The median time interval between biopsy and PET/CT scan was 34.5 days (range 15-117 days). The median PSA value of the patients was 6.8 ng/ml (range 1.0-38.7 ng/ml). The images as well as the histologic specimen were analyzed on a sextant basis. Standardized uptake value (SUV) mean and SUV max were calculated in each segment and the results were correlated with the result of histology respectively. Additionally, the tumor configuration in the histologic specimen was classified in 4 groups: 1=unifocal, 2=multifocal, 3=rindlike, 4=size<5mm. The influence of BPH, prostatitis, HGPIN and PCa as well as of T-stage and Gleason score on the SUV was calculated using a linear model.
Eur Urol Suppl 2011;10(2):64
Results: Overall 2,526 segments were analyzed with a median SUV mean of 3.3 (range: 0.8-15.0). In 602/2,526 segments PCa tissue was present with a median SUV mean of 3.4 (range: 1.0-15.0) The SUV mean in segment basis was 4% higher when PCa was present compared to BPH, prostatitis or HGPIN (p<0.001). In the 6/43 pts with T3-stage SUV mean was 12% higher than in the 37/43pts with T2-stage (p=0.027). There was no influence of the Gleason score on the SUV. The tumor configuration in histology was classified as 1 in 21, as 2 in 9, as 3 in 5 and as 4 in 8 pts. PCa could not be detected in 15/43 (35%) pts (all T2-stage, 8/8 classified as 4, 2/5 classified as 3, 1/9 classified as 2, 3/21 classified as 1 in the histologic specimen). Conclusions: The detection and localization of PCa in the prostate with [11C] choline-PET/CT is affected by the tumor configuration. Small and in part rind-like tumors could not be visualized -most likely- due to partial volume effects. Therefore, our data do not support the routine use of PET/CT with [11C]-Choline as a first-line screening procedure for prostate cancer in men at risk.
125
Detection of CEACAM1 and CEA in urine samples of prostate cancer patients
Tilki D.1, Behrend A.1, Bernhard B.B.2, Seitz M.1, Stief C.G.1, Ergün S.2, Reich O.3 1 Ludwig-Maximilians-University Munich, Dept. of Urology, Munich, Germany, 2 University Hospital Essen, Institute of Anatomy, Essen, Germany, 3Klinikum Harlaching, Dept. of Urology, Munich, Germany Introduction & Objectives: CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is expressed in normal prostate epithelium and angiogenicly activated endothelial cells (EC) where it exhibits pro-angiogenic properties. Also CEA is expressed in several normal epithelia. We recently reported the detection of soluble CEACAM1 in human urine samples and identified it as a potential diagnostic marker for bladder cancer. The aim of this study was to evaluate the value of urinary CEACAM1 and CEA for detection of prostate cancer (PCa). Materials & Methods: Totally, 145 patients were included in this prospective study. Immunohistochemistry for CEACAM1 and CEA was performed on paraffin sections obtained from 10 normal prostate specimens and 20 PCa specimens. ELISA for CEACAM1 and CEA was performed on urine samples of healthy volunteers, patients with BPH, severe cystitis, and prostate cancer. Results: CEACAM1 immunostaining in normal prostate epithelium disappears in prostate cancer while it appears in EC of adjacent vessels. CEA immunostaining shows a strong staining in normal prostate glands and was also strongly present in the lumina of prostate glands. ELISA analysis revealed that urinary CEACAM1 levels were significantly higher in PCa patients compared to control subjects (mean: 234.83 vs 90.06 ng/ml, p<0.001) and that urinary CEA levels were significantly lower in PCa patients compared to control subjects (mean: 1,115 vs 0,539 ng/ml, p=0.013). The area under the curve for PCa detection was 0,689 (95% CI: 0.6020.776) for CEACAM1 and 0.330 (95% CI: 0.241-0.418) for CEA. Conclusions: Urinary CEACAM1 and CEA levels discriminate PCa patients from non-PCa subjects. Larger studies are necessary to establish the diagnostic and prognostic role of these potentially novel urinary markers in PCa.
126
Exponential PSA trends predict the risk of high Gleason cancer two years into the Future for a screening population
Bektic J., Klocker H., Steiner E., Stenzel B., Skradski V., Horninger W., Neville T.B. Medical University Innsbruck, Dept. of Urology, Innsbruck, Austria Introduction & Objectives: We hypothesized that trends in PSA could predict future risks of high Gleason cancer and justify low PSA thresholds for high PSA growth rates. Materials & Methods: 468 men had adequate PSA history (at least 5 PSA tests over at least 4 years and no more than 2 years between). 137 men were diagnosed with cancer, treated with RP and had pathology Gleason scores recorded. These RP patients were divided into High Gleason and Low Gleason groups. There were 25 men with High Gleason (defined as 4+3 plus 8–10). 331 men were not diagnosed with cancer. The annual growth rate in cancer PSA (PSAgr) was estimated using a consistent exponential trend plus no-cancer baseline. Cancer PSA was estimated as the difference between the trend and the baseline. Consistent trends were fit using the full history and also excluding the last two years to test predictive power. The data was divided into high and low PSAgr groups. Each of those groups was divided into high and low cancer PSA groups. The probability of high Gleason cancer was calculated for each group. Results: The probability of high Gleason cancer was higher for high PSAgr trends than for low PSAgr trends (one sided p value of 0.0038 using the full history and 0.0015 for the two year prediction). The probability increased more steeply with increasing cancer PSA for high PSAgr than for low PSAgr. At cancer PSA of 3.0 the two-year prediction of risk was 2.0 times the full history.
123
Engrailed-2 (EN2): A highly specific urinary biomarker for the early diagnosis of prostate cancer
Morgan R.M.1, Ismail M.1, Boxall A.1, Bhaat A.1, Hindley R.2, Michael A.1, Langley S.M.3, Zylstra J.1, Pandha H.S.1 1 Postgraduate Medical School, Dept. of Urological Oncology, Guildford, United Kingdom, 2Basingstoke Hospital, Dept. of Urology, Basingstoke, United Kingdom, 3 Royal Surrey Hospital, Dept. of Urology, Guildford, United Kingdom Introduction & Objectives: Despite recent publication of numerous putative biomarkers of prostate cancer (PC)and the development of 'risk models' we are still completely dependent clinically on serum PSA. There is therefore an urgent need for new diagnostic biomarkers and particularly those identifying 'significant cancers' . A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, have to be overcome such as raised levels in non-cancer disorders of the prostate . We have assessed the diagnostic potential of EN2 protein, a homeodomain-containing transcription factor expressed in PC cell lines, prostate cancer tissue and secreted into the urine by PC in men. Materials & Methods: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine (without prior digital rectal examination (DRE)) was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n=82) and controls (n=102). Controls included men with high PSA who were biopsy negative as well as low PSA with no symptoms or family history recruited from a 'well man' health screening program. Results: EN2 expression was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. We evaluated tissue from our clinical cases in our practice and large PC tissue arrays. EN2 is stable in urine for 4 days at room temperature. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results we confirmed independently by evaluation of men with PC and controls from a second academic centre at Cambridge University. Conclusions: This study evaluated a transcription factor secreted by PC as a simple ELISA test without the requirement for DRE. Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. The high sensitivity, specificity and stability of EN2 at room temperature would make this test attractive as a simple screening tool in the community. The lack of requirement for DRE and its stability differentiates it from other tests currently under evaluation. The ELISA test used for EN2 detection can be simply converted to a lateral flow or 'dipstick' format for ease of use potentially in the primary care setting. A larger multicentre study to further evaluate the diagnostic and monitoring potential of EN2 is justified.
124
Tumor configuration of prostate cancer (PCa) influences the sensitivity of [11C]choline positron emission tomography/computed tomography (PET/CT)
Maurer T.1, Souvatzoglou M.2, Weirich G.3, Schwarzenboeck S.2, Schuster T.4, Herrmann K.2, Kübler H.1, Wester H.J.2, Gschwend J.E.1, Schwaiger M.2, Krause B.J.2, Treiber U.1 1 Technical University Munich, Dept. of Urology, Munich, Germany, 2Technical University Munich, Dept. of Nuclear Medicine, Munich, Germany, 3Technical University Munich, Institute of Pathology, Munich, Germany, 4Technical University Munich, Institute of Medical Statistics and Epidemiology, Munich, Germany Introduction & Objectives: The purpose of this prospective study was to evaluate the diagnostic efficacy of [11C] choline-PET/CT in differentiating PCa from highgrade prostatic intraepithelial neoplasia (HGPIN), benign prostate hyperplasia (BPH) and prostatitis and for detecting and localising PCa in the prostate with respect to tumor configuration in the histologic specimen. Materials & Methods: 43 patients with biopsy proven PCa underwent radical prostatectomy after [11C] choline PET/CT. The median time interval between biopsy and PET/CT scan was 34.5 days (range 15-117 days). The median PSA value of the patients was 6.8 ng/ml (range 1.0-38.7 ng/ml). The images as well as the histologic specimen were analyzed on a sextant basis. Standardized uptake value (SUV) mean and SUV max were calculated in each segment and the results were correlated with the result of histology respectively. Additionally, the tumor configuration in the histologic specimen was classified in 4 groups: 1=unifocal, 2=multifocal, 3=rindlike, 4=size<5mm. The influence of BPH, prostatitis, HGPIN and PCa as well as of T-stage and Gleason score on the SUV was calculated using a linear model.
Eur Urol Suppl 2011;10(2):64
Results: Overall 2,526 segments were analyzed with a median SUV mean of 3.3 (range: 0.8-15.0). In 602/2,526 segments PCa tissue was present with a median SUV mean of 3.4 (range: 1.0-15.0) The SUV mean in segment basis was 4% higher when PCa was present compared to BPH, prostatitis or HGPIN (p<0.001). In the 6/43 pts with T3-stage SUV mean was 12% higher than in the 37/43pts with T2-stage (p=0.027). There was no influence of the Gleason score on the SUV. The tumor configuration in histology was classified as 1 in 21, as 2 in 9, as 3 in 5 and as 4 in 8 pts. PCa could not be detected in 15/43 (35%) pts (all T2-stage, 8/8 classified as 4, 2/5 classified as 3, 1/9 classified as 2, 3/21 classified as 1 in the histologic specimen). Conclusions: The detection and localization of PCa in the prostate with [11C] choline-PET/CT is affected by the tumor configuration. Small and in part rind-like tumors could not be visualized -most likely- due to partial volume effects. Therefore, our data do not support the routine use of PET/CT with [11C]-Choline as a first-line screening procedure for prostate cancer in men at risk.
125
Detection of CEACAM1 and CEA in urine samples of prostate cancer patients
Tilki D.1, Behrend A.1, Bernhard B.B.2, Seitz M.1, Stief C.G.1, Ergün S.2, Reich O.3 1 Ludwig-Maximilians-University Munich, Dept. of Urology, Munich, Germany, 2 University Hospital Essen, Institute of Anatomy, Essen, Germany, 3Klinikum Harlaching, Dept. of Urology, Munich, Germany Introduction & Objectives: CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is expressed in normal prostate epithelium and angiogenicly activated endothelial cells (EC) where it exhibits pro-angiogenic properties. Also CEA is expressed in several normal epithelia. We recently reported the detection of soluble CEACAM1 in human urine samples and identified it as a potential diagnostic marker for bladder cancer. The aim of this study was to evaluate the value of urinary CEACAM1 and CEA for detection of prostate cancer (PCa). Materials & Methods: Totally, 145 patients were included in this prospective study. Immunohistochemistry for CEACAM1 and CEA was performed on paraffin sections obtained from 10 normal prostate specimens and 20 PCa specimens. ELISA for CEACAM1 and CEA was performed on urine samples of healthy volunteers, patients with BPH, severe cystitis, and prostate cancer. Results: CEACAM1 immunostaining in normal prostate epithelium disappears in prostate cancer while it appears in EC of adjacent vessels. CEA immunostaining shows a strong staining in normal prostate glands and was also strongly present in the lumina of prostate glands. ELISA analysis revealed that urinary CEACAM1 levels were significantly higher in PCa patients compared to control subjects (mean: 234.83 vs 90.06 ng/ml, p<0.001) and that urinary CEA levels were significantly lower in PCa patients compared to control subjects (mean: 1,115 vs 0,539 ng/ml, p=0.013). The area under the curve for PCa detection was 0,689 (95% CI: 0.6020.776) for CEACAM1 and 0.330 (95% CI: 0.241-0.418) for CEA. Conclusions: Urinary CEACAM1 and CEA levels discriminate PCa patients from non-PCa subjects. Larger studies are necessary to establish the diagnostic and prognostic role of these potentially novel urinary markers in PCa.
126
Exponential PSA trends predict the risk of high Gleason cancer two years into the Future for a screening population
Bektic J., Klocker H., Steiner E., Stenzel B., Skradski V., Horninger W., Neville T.B. Medical University Innsbruck, Dept. of Urology, Innsbruck, Austria Introduction & Objectives: We hypothesized that trends in PSA could predict future risks of high Gleason cancer and justify low PSA thresholds for high PSA growth rates. Materials & Methods: 468 men had adequate PSA history (at least 5 PSA tests over at least 4 years and no more than 2 years between). 137 men were diagnosed with cancer, treated with RP and had pathology Gleason scores recorded. These RP patients were divided into High Gleason and Low Gleason groups. There were 25 men with High Gleason (defined as 4+3 plus 8–10). 331 men were not diagnosed with cancer. The annual growth rate in cancer PSA (PSAgr) was estimated using a consistent exponential trend plus no-cancer baseline. Cancer PSA was estimated as the difference between the trend and the baseline. Consistent trends were fit using the full history and also excluding the last two years to test predictive power. The data was divided into high and low PSAgr groups. Each of those groups was divided into high and low cancer PSA groups. The probability of high Gleason cancer was calculated for each group. Results: The probability of high Gleason cancer was higher for high PSAgr trends than for low PSAgr trends (one sided p value of 0.0038 using the full history and 0.0015 for the two year prediction). The probability increased more steeply with increasing cancer PSA for high PSAgr than for low PSAgr. At cancer PSA of 3.0 the two-year prediction of risk was 2.0 times the full history.