title: Molecular staging of pelvic surgical margins after radical prostatectomy: comparison of RT-PCR for prostate-specific antigen and telomerase activity.
abstract: The further course of prostate cancer (PC) after radical prostatectomy (RPX) is decisively influenced by the local tumor stage. Although it is now possible to assess the risk of local recurrence from the histopathology, precise predictions cannot be made. A more accurate evaluation would be desirable, mainly for early planning of adjuvant therapy. We assessed the detection of telomerase activity using the Telomeric Repeat Amplification Protocol in surgical margins compared to RT-PCR-supported prostate-specific antigen (PSA) mRNA detection and conventional histopathological examination. We examined 95 patients with local PC during RPX and 16 patients with muscle-invasive transitional bladder cancer who underwent radical cystectomy. After RPX or RCX biopsies were obtained from 4 or 3 defined areas of the prostatic fossa and processed by TRAP assay for telomerase activity and by RT-PCR for PSA using a standard protocol. Five of 48 patients (10.4%) with organ-confined prostate cancer (pT2) and 7 of 47 patients (14.9%) with locally advanced PC (>pT2) had positive detection of telomerase activity in at least one positive specimen. In contrast to RT-PCR for PSA mRNA and histological findings for organ-confined and locally advanced disease, detection of telomerase activity yielded no statistically significant correlation to clinical parameters. Only PC-patients with positive histopathological margins had a positive correlation between detection of telomerase activity and high Gleason scores (r=0.65, p=0.022). Based on the results obtained and the current state of knowledge, measurement of telomerase activity must be considered less sensitive than RT-PCR for PSA mRNA in surgical margins, although tumor specificity should theoretically be higher. It is not even sure at the present time whether a combination of both methods offers any recognizable advantage over PSA mRNA detection alone. The value of the results obtained in this study will have to be assessed in a further follow-up to determine whether patients with positive molecular detection have an increased risk of local recurrence.
authors.affiliation: Department of Urology, Klinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany. straub@medizin.fu-berlin.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Straub
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Carsten
authors.initials: C
authors.lastname: Goessl
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Heicappell
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
mesh_terms: D000368:Aged; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000096:biosynthesis*; D016615:Telomere / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019098:Telomerase; D017430:Prostate-Specific Antigen