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.

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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.

BackgroundThe pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX.MethodsThe document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy.ResultsThe pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern.ConclusionscMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis.

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No association was observed between the grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate.

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