Prostatic Neoplasms: Semjonow A

Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Holten-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih IeM, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP, Anonymous00039. · Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK. · Clin Chem. · Pubmed #19042984 No free full text.

Abstract: BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast, and ovarian--were critically reviewed. RESULTS: For testicular cancer, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. alpha-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is <10 microg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node-negative patients. CA15-3/BR27-29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer. CONCLUSIONS: Implementation of these recommendations should encourage optimal use of tumor markers.

Semjonow A. · No affiliation provided · Eur Urol. · Pubmed #19209420 No free full text.

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Semjonow A, Schmid HP. · · Urol Res. · Pubmed #12086020 No free full text.

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Hammerer P, Semjonow A. · No affiliation provided · Urologe A. · Pubmed #10957769 No free full text.

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Sölétormos G, Semjonow A, Sibley PE, Lamerz R, Petersen PH, Albrecht W, Bialk P, Gion M, Junker F, Schmid HP, Van Poppel H. · Department of Clinical Biochemistry, Hillerød Hospital, Hillerød, Denmark. · Clin Chem. · Pubmed #15961552 links to  free full text

Abstract: BACKGROUND: The objectives of this study were to determine whether a single result for total prostate-specific antigen (tPSA) can be used confidently to guide the need for prostate biopsy and by how much serial tPSA measurements must differ to be significant. tPSA measurements include both analytical and biological components of variation. The European Group on Tumor Markers conducted a literature survey to determine both the magnitude and impact of biological variation on single, the mean of replicate, and serial tPSA measurements. METHODS: The survey yielded 27 studies addressing the topic, and estimates for the biological variation of tPSA could be derived from 12 of these studies. RESULTS: The mean biological variation was 20% in the concentration range 0.1-20 microg/L for men over 50 years. The biological variation means that the one-sided 95% confidence interval (CI) of the dispersion for a single tPSA result is approximately 33%. Three replicate samples with one analysis on each narrow the one-sided 95% CI for the mean concentration to approximately 20% and facilitate decisions on prostate biopsy. During monitoring of serial measurements, the change needed for significance is approximately 50% (P <0.05). CONCLUSIONS: The biological variation of tPSA has implications for screening, diagnosis, and monitoring. Single measurements may not be sufficiently precise for screening and diagnosis. Replicate samples and calculation of the mean concentration may improve precision by reducing the dispersion. Monitoring of tPSA requires an estimate of either the change needed for significance or, alternatively, of the significance of the change.

Schmid HP, Prikler L, Semjonow A. · Department of Urology, Kantonsspital, 9007 St. Gallen, Switzerland. · Recent Results Cancer Res. · Pubmed #12903857 No free full text.

Abstract: The effect of population screening with regard to reduction of prostate cancer specific mortality and quality of life issues is not yet clear. Several national and international prospective studies are currently being conducted to answer these important questions. They include the trials in the Federal State of Tyrol, Austria and in the Quebec City area, Canada, as well as the Prostate, Lung, Colorectal and Ovarian (PLCO) trial in the United States and the European Randomized Study of Screening for Prostate Cancer (ERSPC). In the meantime, individual case finding (opportunistic screening) is recommended for men with a life-expectancy of at least 10 years.

Schmid HP, Semjonow A, Aus G, Hertle L. · Department of Urology, Westfälische Wilhelms-University, Münster, Germany. · Urol Int. · Pubmed #11025425 No free full text.

Abstract: Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy or radiation therapy for clinically localized prostate cancer has regained interest in recent years but proof of its clinical benefit with respect to patient survival is still pending. We reviewed the literature regarding NHT in prostate cancer; only studies with a high evidence level were included for analysis. Five prospective randomized trials of NHT in radical prostatectomy-treated patients could be identified. Despite significantly lower numbers of positive surgical margins in the NHT group, prostate specific antigen failure rates were similar in the NHT group and the surgery only group. Data on disease-free and overall survival are not yet available. The two prospective randomized studies of NHT in radiation-treated patients could demonstrate better local control of the tumor in the NHT group. However, there was no difference in overall survival between the NHT arm and the radiation only arm. Future clinical research should consider type and duration of hormonal treatment and evaluate potential surrogate end points. To date, there is no hard evidence in favor of NHT prior to radical prostatectomy or external beam irradiation. NHT in prostate cancer should only be applied within controlled trials.

Semjonow A, De Angelis G, Oberpenning F, Schmid HP, Brandt B, Hertle L. · Department of Urology and Institute of Clinical Chemistry and Laboratory Medicine, Westfälische Wilhelms-Universität, Münster, Germany. · BJU Int. · Pubmed #10971300 No free full text.

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De Angelis G, Brandt B, Schmid HP, Semjonow A. · Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität, Münster. · Urologe A. · Pubmed #10957771 No free full text.

Abstract: The determination of prostate-specific antigen is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and current status of prostate-specific antigen in tumor diagnostics.

Lein M, Semjonow A, Graefen M, Kwiatkowski M, Abramjuk C, Stephan C, Haese A, Chun F, Schnorr D, Loening SA, Jung K. · Departments of Urology, University Hospital Charité, Humboldt University Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany. · J Urol. · Pubmed #16280753 No free full text.

Abstract: PURPOSE: The determination of pro prostate specific antigen (proPSA) forms has been suggested to be promising in prostate cancer diagnosis. In this multicenter trial we evaluated the diagnostic usefulness of (-5, -7) proPSA. MATERIALS AND METHODS: A total of 2,055 white men, including 1,046 with and 1,009 without prostate cancer, with total PSA (tPSA) between 0.28 and 81 ng/ml were retrospectively analyzed. Of these men 2,026 and 1,727 had tPSA less than 20 and less than 10 ng/ml, respectively. All subjects were untreated for prostatic disease and underwent multisector needle biopsy of the prostate. An Elecsys 2010 analyzer was used to determine tPSA, free PSA (fPSA) and (-5, -7) proPSA in the 2,055 serum samples. ROC analyses were performed to discriminate men with biopsy positive and negative results in the entire and in select tPSA ranges. RESULTS: In the select tPSA range 2 to 4 ng/ml the area under the ROC curve for proPSA (0.53) and proPSA/fPSA (0.59) was not significantly larger than that for tPSA (0.60) or the fPSA/tPSA (f/tPSA) ratio (0.64). In the tPSA range 4 to 10 ng/ml the area under the curve for the ratio proPSA/fPSA (0.67) was larger than for tPSA (0.53) but not larger than for f/tPSA (0.69). The f/tPSA ratio demonstrated the best discriminatory power in this tPSA range of 4 to 10 ng/ml. CONCLUSIONS: In this multicenter study no improvement in diagnostic accuracy was shown when comparing (-5, -7) proPSA and the corresponding ratios with tPSA or f/tPSA. Further studies using other proPSA forms or tumor associated proteins should be done.

Lein M, Jung K, Hammerer P, Graefen M, Semjonow A, Stieber P, Ossendorf M, Luboldt HJ, Brux B, Stephan C, Schnorr D, Loening SA. · Department of Urology, University Hospital Charité, Humboldt University, Berlin, Germany. · Prostate. · Pubmed #11340629 No free full text.

Abstract: BACKGROUND: The aim was to evaluate the clinical performance of alpha(1)-antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of prostate cancer (PCa) in a multicenter trial. METHODS: Three hundred sixty-seven white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA concentrations between 2 and 20 microg/L were analyzed. The Elecsys system 2010 (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system (Roche Diagnostics). RESULTS: The median concentrations of tPSA (PCa: 8.43 microg/L vs. BPH: 6.60 microg/L) and PSA-ACT (8.30 microg/L vs. 6.46 microg/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different. Receiver operating characteristics (ROC) analysis for discrimination between PCa and BPH (tPSA between 2 and 20 microg/L) was performed with 252 matched pairs and showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA between 4 and 10 microg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65) was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found. CONCLUSIONS: The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did not improve the diagnostic impact in patients undergoing evaluation for PCa compared to fPSA/tPSA ratio.

Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Störkel S, Willich N, Semjonow A, Souchon R, Stöckle M, Rübe C, Weissbach L, Althaus P, Rebmann U, Kälble T, Feldmann HJ, Wirth M, Hinke A, Hinkelbein W, Miller K. · Department of Radio Oncology, University Hospital Ulm, Ulm, Germany. · J Clin Oncol. · Pubmed #19433689 No free full text.

Abstract: PURPOSE: Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP. METHODS: After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival. RESULTS: Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%. CONCLUSION: Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.

Breil B, Semjonow A, Dugas M. · Department of Medical Informatics and Biomathematics, University of Münster, Domagkstrasse 9, 48149 Münster, Germany. · BMC Med Inform Decis Mak. · Pubmed #19154600 links to  free full text

Abstract: BACKGROUND: Timely and accurate information is important to guide the medical treatment process. We developed, implemented and assessed an order-entry system to support documentation of prostate histologies involving urologists, pathologists and physicians in private practice. METHODS: We designed electronic forms for histological prostate biopsy reports in our hospital information system (HIS). These forms are created by urologists and sent electronically to pathologists. Pathological findings are entered into the system and sent back to the urologists. We assessed time from biopsy to final report (TBF) and compared pre-implementation phase (paper-based forms) and post-implementation phase. In addition we analysed completeness of the electronic data. RESULTS: We compared 87 paper-based with 86 electronic cases. Using electronic forms within the HIS decreases time span from biopsy to final report by more than one day per patient (p < 0.0001). Beyond the optimized workflow we observed a good acceptance because physicians were already familiar with the HIS. The possibility to use these routine data for quality management and research purposes is an additional important advantage of the electronic system. CONCLUSION: Electronic documentation can significantly reduce the time from biopsy to final report of prostate biopsy results and generates a reliable basis for quality management and research purposes.

Bolenz C, Gierth M, Grobholz R, Köpke T, Semjonow A, Weiss C, Alken P, Michel MS, Trojan L. · Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany. · BJU Int. · Pubmed #19154463 No free full text.

Abstract: OBJECTIVE: To describe the localization and to assess the clinical implications of areas of undetected prostate cancer in radical prostatectomy (RP) specimens, focusing on patients with unilaterally negative preoperative biopsy cores. PATIENTS AND METHODS: The study included 149 of 559 consecutive patients (26.7%) who had RP for prostate cancer. Unilateral prostate cancer was diagnosed from prostate biopsies, taken by several physicians, but > or = pT2c disease was present in the RP specimen. The prostate was dissected by standardized transversal cuts and tumour areas were mapped by one genitourinary pathologist. To estimate the tumour size and location, areas of prostate cancer were transferred to a digital grid database representing the prostate by 794 units. RESULTS: The most frequent location of undetected prostate cancer was in the dorsalateral region and in the apex of the prostate. The mean tumour volume of the false-negative lobe was significantly lower than contralaterally (18.9 vs 47.5 units, P < 0.001). In 36 of 149 patients (24.2%), the tumour volume on the negative biopsy side was equal or higher than on the positive biopsy side; in the final RP specimen, 60 patients (40.3%) had capsular involvement on the negative biopsy side. CONCLUSION: Significantly many patients with newly diagnosed prostate cancer remain clinically understaged. The apical and dorsolateral region of the prostate are not adequately represented in current biopsy strategies. Undetected tumour areas are often clinically significant by size and capsular involvement, indicating a direct clinical implication when planning nerve-sparing RP or focal therapy. Our results show a continuing need for optimized and standardized biopsy protocols.

Oberpenning F, von Knobloch R, Sprute W, Roth S, Rathert M, Bierer S, Gerss J, Semjonow A. · Klinik für Urologie und Kinderurologie, St. Agnes Hospital, Bocholt, Germany. · Urologe A. · Pubmed #18496663 No free full text.

Abstract: BACKGROUND: A novel urine test for early detection of prostate cancer (PCA), distributed and marketed by the company DiaPat, is advertised by the statement "correct analysis in 9 of 10 cases." PATIENTS AND METHODS: The test separates urinary polypeptides by means of capillary electrophoresis and characterizes the peptides in a time-of-flight mass spectrometer. The DiaPat test was performed on the urine of 18 men prior to multiple ultrasound-guided prostate biopsies. RESULTS: Sixteen of the 18 samples met the requirements for sample quality as established by the manufacturer. Eight of these 16 urine samples had been collected from patients in whom biopsies consecutively detected PCA; the remaining eight patients had benign biopsy results. Among the eight patients with detected PCA, the urine test yielded a low probability for PCA in three cases and a high probability in five. Within the group of eight patients with benign biopsy results, the urine test predicted a high probability for PCA in five men and a low probability in three. For the given PCA incidence of 50% within the investigated population, the DiaPat test correctly predicted biopsy results in one half of the population, whereas prediction in the remaining half was incorrect. CONCLUSION: Unless reliable validation of the DiaPat urine test for PCA is available, no clinical consequences should be drawn from the test results.

Kraywinkel K, Lehnert M, Semjonow A, Hense HW. · Epidemiologisches Krebsregister NRW gGmbH, Robert-Koch-Strasse 40, 48149 Münster, Deutschland. · Urologe A. · Pubmed #18398595 No free full text.

Abstract: BACKGROUND: Prostate cancer is characterized by worldwide increasing incidence rates, improved survival, and decreasing mortality. We investigated the current situation in the Epidemiological Cancer Register of the District of Münster, Germany (which has approximately 1.25 million male inhabitants). MATERIALS AND METHODS: We calculated the incidence and mortality rates, stage distribution, and relative survival rates for prostate cancer between the years 2002 and 2004. RESULTS: The age-standardized incidence rate was 115/100,000 men per year, and the median age at diagnosis was 70 years. The tumour stage was T1/T2 in 69.6% of cases. The estimated relative survival after 5 years was 83.5% (95% confidence interval 81.4-85.4) and after 10 years was 73.3% (69.5-77.0). Survival was barely affected when the tumour was limited to the prostate (UICC I-II), whereas survival rates were markedly reduced when the tumour had spread or had infiltrated adjacent structures (UICC IV; relative 10-year survival rate 22.1%). CONCLUSIONS: The majority of patients with prostate cancer now have a favourable prognosis. Increased incidence rates must be interpreted in the context of widespread use of prostate-specific antigen testing.

Bettendorf O, Schmidt H, Staebler A, Grobholz R, Heinecke A, Boecker W, Hertle L, Semjonow A. · Institute of Pathology, University of Münster, Münster, Germany. · Genes Chromosomes Cancer. · Pubmed #18383208 No free full text.

Abstract: Recent studies have shown that intraductal prostate carcinoma (IDC-P) should be considered as a separate lesion distinct from prostatic intraepithelial neoplasia (PIN). The purpose of the present study was to analyze the genetic relationship between benign prostatic tissue, PIN, invasive cancer, IDC-P, and extracapsular tumor tissue to get further information about the role of IDC-P in the development of prostate cancer. One hundred five radical prostatectomy specimens were investigated immunohistochemically, 77 cases were analyzed by PCR for LOH of the tumor suppressor genes TP53 and RB1, and 11 cases of IDC-P and 10 cases of PIN were investigated using comparative genomic hybridization (CGH). At CGH analysis, IDC-P showed several chromosomal imbalances in contrast to PIN, where no changes were found. We could demonstrate a significant increase of LOH for TP53 or RB1 from benign tissue to PIN. LOH of both TP53 and RB1 were frequently found in IDC-P (52%), followed by extracapsular tumor tissue (44%), invasive cancer (24%), PIN (19%), and benign prostatic tissue (17%). Increased immunohistochemical expression was found in invasive cancer for TP53, RB1, and for PTEN. Decreased expression could be demonstrated in extracapsular tumor tissue and in IDC-P. Our results indicate that IDC-P in general follows the genetic pathway from normal epithelium over PIN lesion. IDC-P represents a separate prostatic lesion and should be graded as a poorly differentiated carcinoma.

Schmidt H, Semjonow A, Csiszar K, Korsching E, Brandt B, Eltze E. · Gerhard Domagk Institut für Pathologie, Universitäitsklinikum Münster. · Verh Dtsch Ges Pathol. · Pubmed #18314628 No free full text.

Abstract: Various microsatellite and CGH studies in prostate cancer identify deletions on the short arm of chromosome 8 especially at band 8p21-22 searching for unknown putative tumor suppressor genes. By means of microsatellite markers several candidate genes were detected which may play different roles in early prostate cancer progression. We established a quantitative gene dosage PCR based on the real time PCR method serving the purpose of genomic fine mapping. Therefore we used 10 Assays-on Demand (ABI) for the detection of deletions located between and nearby the microsatellite markers D8S258 and NEFL spanning a genomic region of approximate 7 mbp. Comparative immunohistochemical analysis from tissue micro arrays (TMA) of 1122 independent cases followed. We were able to detect three clearly separated deletion intervals on 8p21-22. One on LZTS1, second on NEFL and third a deletion hot spot on LOXL2, which was affected in 72% of all investigated cases. Our comparative immunohistochemical TMA based studies demonstrate that LOXL2 is nearly lost in most prostate cancer tissues. LOXL2 catalyze the crosslinking of collagen and elastin in the extracellular matrix and it has been assumed that it is involved in tumor suppression and cell adhesion. LOXL2 is frequently expressed in proliferating tissues and shows a high expression in benign prostate tissue too. In prostate cancer the expression is positive correlated with the MIB1-score.

Ronquist KG, Carlsson L, Ronquist G, Semjonow A, Wülfing C, Larsson A. · Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden. · Scand J Clin Lab Invest. · Pubmed #17926197 No free full text.

Abstract: OBJECTIVE: Clusterin is a ubiquitous secretory sulphated glycoprotein present in prostasomes. It is an anti-apoptotic mediator in prostate cancer and is among the most frequently occurring prostasomal proteins immunogenic in prostate cancer patients. The aim of the present study was to investigate the occurrence of anti-clusterin antibodies in the serum of patients with prostate cancer and whether there is a relationship between anti-clusterin antibody titres and other clinico-pathological variables. MATERIAL AND METHODS: Serum samples were collected from 391 consecutive patients with suspected prostate cancer (150 benign prostate and 241 prostate cancer). The patients' serum samples were used in an ELISA where microtitre wells were coated with purified clusterin from serum of a healthy volunteer. Flow cytometric studies of clusterin and prostasomes were performed. RESULTS: Flow cytometric analyses revealed the presence of clusterin on the surface of seminal prostasomes. Anti-clusterin ELISA titres in sera of patients did not differ significantly from those of a control group. A significant "inverse" correlation existed between anti-clusterin ELISA titres and lymph node metastases (p = 0.047), but only 11 out of 161 patients had metastases. These titres correlated significantly with total prostate (p = 0.021) and transitional zone (p = 0.015) volumes of the patients. CONCLUSIONS: The correlation between serum anti-clusterin antibody titres and other clinico-pathological variables was generally weak in prostate cancer patients, although clusterin has been assigned an important role in tumourigenesis and progression of prostate cancer. However, the anti-clusterin antibody titre appeared to be related to prostate volume, correlating to both transitional zone volume and total volume of the prostate.

Cottrell S, Jung K, Kristiansen G, Eltze E, Semjonow A, Ittmann M, Hartmann A, Stamey T, Haefliger C, Weiss G. · Epigenomics, Inc., Seattle, Washington, USA. · J Urol. · Pubmed #17437806 No free full text.

Abstract: PURPOSE: About 15% of men experience prostate specific antigen recurrence after radical prostatectomy. A DNA methylation based molecular test could provide important information to predict which patients are most likely to experience recurrence. MATERIALS AND METHODS: We performed a genome-wide scan to find aberrantly methylated loci in prostate cancer from patients with early recurrence, high Gleason score or advanced stage. We discovered 441 candidate methylation markers and further analyzed 62 candidates in a methylation microarray study of 304 frozen prostatectomy samples. RESULTS: Methylation of 25 markers was significantly changed in high Gleason score (8-10) vs low Gleason score (2-6) cancers. Methylation levels of the 3 marker candidates GPR7, ABHD9 and an expressed sequence tag on chromosome 3 (Chr3-EST) were significantly increased in patients who did vs did not experience early PSA recurrence (Bonferroni correction p<0.05). Furthermore, these markers were also informative when the sample set was restricted to 68 mid range Gleason score (6 or 7) samples only. We developed real-time polymerase chain reaction assays for ABHD9 and Chr3-EST, and measured methylation in paraffin embedded, formalin fixed prostatectomy samples from an independent set of 223 patients. Methylation of the 2 markers was significantly higher in patients with early PSA recurrence compared to that in patients who did not experience PSA recurrence. CONCLUSIONS: We report that methylation of the 3 novel markers GPR7, ABHD9 and Chr3-EST is significantly associated with prostate cancer prognosis. Incorporation of these methylation markers into clinical practice will result in more accurate prediction of which patients are likely to experience PSA recurrence.

Stephan C, Xu C, Cammann H, Graefen M, Haese A, Huland H, Semjonow A, Diamandis EP, Remzi M, Djavan B, Wildhagen MF, Blijenberg BG, Finne P, Stenman UH, Jung K, Meyer HA. · Department of Urology, Charité-Universitätsmedizin Berlin, CCM, Berlin, Germany. · World J Urol. · Pubmed #17333205 No free full text.

Abstract: Use of percent free PSA (%fPSA) and artificial neural networks (ANNs) can eliminate unnecessary prostate biopsies. In a total of 4,480 patients from five centers with PSA concentrations in the range of 2-10 ng/ml an IMMULITE PSA-based ANN (iANN) was compared with other PSA assay-adapted ANNs (nANNs) to investigate the impact of different PSA assays. ANN data were generated with PSA, fPSA (assays from Abbott, Beckman, DPC, Roche or Wallac), age, prostate volume, and DRE status. In 15 different ROC analyses, the area under the curve (AUC) in the PSA ranges 2-4, 2-10, and 4-10 ng/ml for the nANN was always significantly larger than the AUC for %fPSA or PSA. The nANN and logistic regression models mostly also performed better than the iANN. Therefore, for each patient population, PSA assay-specific ANNs should be used to optimize the ANN outcome in order to reduce the number of unnecessary biopsies.

Bettendorf O, Oberpenning F, Köpke T, Heinecke A, Hertle L, Boecker W, Semjonow A. · Institute of Pathology, University of Münster, Domagkstrasse 17, 48149 Münster, Germany. · Eur J Surg Oncol. · Pubmed #17175129 No free full text.

Abstract: INTRODUCTION: Tumor volume is one of the best documented prognostic factors for prostate cancer. There are several methods to gain this important parameter but unfortunately most of the clinicians in the world do not get this information in their routine practice from the pathologist. We developed a standardized method to handle radical prostatectomy specimens including a special form of mapping in order to document relevant morphological data. The aim of this study was to investigate if our model of mapping prostate cancer, which we use in routine practice, may serve for visual estimation of tumor volume. METHODS: We estimated the tumor volume of prostate cancer by visual estimation of 350 maps of radical prostatectomy specimens and correlated these data with established prognostic parameters and clinical outcome. RESULTS: Significant correlations between tumor volumes, as obtained from our mapping, and known prognostic parameters such as preoperative serum levels of prostatic specific antigen, loss of differentiation, histological grade, lymph node metastasis, and margins were found. In a multivariate analysis, only Gleason score and tumor stage were shown to be independent prognostic parameters. DISCUSSION: We demonstrate that mapping of prostate cancer is more than a simple method of documentation but may serve as a method for visual estimation of tumor volume of prostate cancer after radical prostatectomy. This method can further be used for a visual documentation of the tumor stage independent of changes in the TNM classification. The method is inexpensive and practicable and can therefore be applied in routine surgical pathology.

Schmidt H, DeAngelis G, Eltze E, Gockel I, Semjonow A, Brandt B. · Prostate Center, University Clinic, University of Münster, Münster, Germany. · Cancer Res. · Pubmed #16982734 links to  free full text

Abstract: The clinical value of prostate-specific antigen (PSA)-positive circulating tumor cells (CTCs) is still a matter of debate and it is also still unclear if these CTCs actually represent the primary tumor. Therefore, we isolated PSA-positive CTCs from the peripheral blood of patients suffering from multifocal cancers and did genetic profiling of each cancer focus by a multiplex PCR-based microsatellite analysis (D7S522, D8S522, NEFL, D10S541, D13S153, D16S400, D16S402, D16S422, and D17S855). In 17 of 20 prostate cancer cases, the loss of heterozygosity (LOH) pattern of the CTCs was identical with only one focus of the primary tumor. Moreover, in six cases, the LOH pattern suggested that smaller foci, down to 0.2 cm3, might deliver CTCs. Interestingly, the highest number of LOHs was observed at the marker D10S541 (85%), the PTEN gene, which was observed much less frequently in unifocal prostate cancer (48%). Furthermore, the infrequently occurring LOH in the BRCA1 gene (38%) was found in four of the five cases where a biochemical recurrence was seen within 3 years after prostatectomy. Therefore, the data might support the assumption that CTCs in prostate cancer are derived from distinct foci of a primary tumor. The size of the tumor focus is not related to the delivery of cells. Although the number of cases that were investigated in this study was small, it might be suggested that the LOH at distinct markers such as D10S541 and D17S855 represent the genes PTEN and BRCA1, which might be associated with the occurrence of CTCs in the peripheral blood of patients as well as an early biochemical recurrence.

Larsson A, Ronquist G, Wülfing C, Eltze E, Bettendorf O, Carlsson L, Nilsson BO, Semjonow A. · Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Uppsala, Sweden. · Urol Oncol. · Pubmed #16678048 No free full text.

Abstract: Prostasomes are secretory granules synthesized, stored, and secreted by normal and neoplastic human prostate epithelial cells. In prostate cancer, they are anticipated to be released into the blood circulation where they may be immunogenic. The aim of our study was to examine whether prostasome antibody presence in serum bears any prognostic significance for men with prostate cancer. We developed a sensitive and specific immunoassay (enzyme-linked immunosorbent assay) to establish the presence of antiprostasome antibodies in serum. The antiprostasome antibody titer in serum, sampled before any kind of therapy for prostate cancer, was examined together with clinicopathologic variables and outcome over a median follow-up of 350 days in 218 patients with verified prostate cancer. We detected these antibodies in 191 (88%) of these patients. This antibody titer did not correlate to serum values of prostate-specific antigen. Significant, inverse relationships were registered for antiprostasome antibody titer, and metastases to bone and/or lymph nodes (P = 0.035) and pT (P = 0.025). These results indicate that the antiprostasome antibody titer in serum may be a novel marker for prostate cancer liability to metastasize.

Theodorescu D, Fliser D, Wittke S, Mischak H, Krebs R, Walden M, Ross M, Eltze E, Bettendorf O, Wulfing C, Semjonow A. · Paul Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, VA 22908, USA. · Electrophoresis. · Pubmed #15981297 No free full text.

Abstract: We describe the use of capillary electrophoresis (CE) coupled with mass spectrometry (MS) to identify single polypeptides and patterns of polypeptides specific for prostate cancer (CaP) in human urine. Using improved sample preparation methods that enable enhanced comparability between different samples, we examined samples from 47 patients who underwent prostate biopsy. Of this group, 21 patients had benign pathology and 26 with CaP, and these were used to define potential biomarkers, which allow discrimination between these two states. In addition, CE-MS data from these 47 urine samples were compared to that of 41 young men (control) without known or suspected clinical CaP to further confirm the polypeptides indicative for CaP. Upon crossvalidation of the same samples, several polypeptides were selected that enabled correct classification of the CaP patients with 92% sensitivity and 96% specificity. We then examined an additional 474 samples from patients with renal disease enrolled in other studies and found that 14 (3%) had polypeptides suggestive of CaP possibly indicating that they harbor clinical CaP. In conclusion, this early pilot study suggests that CE-MS of urine warrants further investigation as a tool that can identify putative biomarkers for CaP.