Reverse transcriptase-polymerase chain reaction for prostate-specific antigen in the molecular staging of pelvic surgical margins after radical prostatectomy
Department of Urology, Klinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany. Urology
(Impact Factor: 2.19).
06/2001; 57(5):1006-11. DOI: 10.1016/S0090-4295(00)01123-7
To examine the application of reverse transcriptase-polymerase chain reaction (RT-PCR) to assist in prostate-specific antigen (PSA) detection in the surgical margins after radical prostatectomy (RP). The risk of local recurrence increases considerably in the presence of extracapsular tumor growth and/or positive surgical margins at RP. Although this makes it possible to identify patients with an increased risk of local recurrence, precise predictions cannot be made. A more precise assessment is desirable mainly for early planning of adjuvant therapy.
Ninety-five patients with clinically organ-confined prostate cancer (CaP) underwent RP. After removing the gland, biopsies were obtained from four defined areas of the prostatic fossa and processed for RT-PCR for PSA detection. Sixteen patients with muscle-invasive bladder carcinoma who underwent radical cystoprostatectomy served as controls.
Thirty-two of 95 patients with CaP (35%) had at least one positive molecular margin indicating an expression for PSA; 19 of 48 (39%) of these had an organ-confined tumor stage according to conventional histology and 13 of 47 (28%) had tumor growth beyond the prostate. A statistically significant correlation between the frequency of positive molecular margins and clinical data was only observed in the group with disease greater than Stage pT2. All controls had negative molecular margins (P = 0.012).
On the basis of the results obtained, molecular diagnostic RT-PCR for PSA detection in the surgical margins after RP seems to be an interesting supplementary tool for monitoring the course and establishing the prognosis. Long-term follow-up of these patients is needed to demonstrate the clinical value of molecular diagnostics of surgical margins during RP.
Available from: Salvatore Blanco
- "To complement pathological staging, new diagnostic and prognostic markers (SHBG , p53, bcl2 Human Callicrein-2, PSMA, and so forth) are under evaluation. Reverse Tanscriptase Polymerase Chain Reaction (RT-PCR) for determination of prostate-specific antigen (PSA) can detect a single prostate cancer cell in a tissue sample [5,6]. The high sensitivity of this technique may increase the accuracy of staging in low tumor burden cases and, consequently, be a more appropriate molecular marker for the determination of the effectiveness of a neoadjuvant therapy such as Maximum Androgenic Blockage (MAB) before radical prostatectomy. "
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We assessed the incidence of micro-metastases at surgical margins (SM) and pelvic lymph nodes (LN) in patients submitted to radical retropubic prostatectomy (RP) after neoadjuvant therapy (NT) or to RP alone. We compared traditional staging to molecular detection of PSA using Taqman-based quantitative real-time PCR (qrt-PCR) never used before for this purpose.
29 patients were assigned to NT plus RP (arm A) or RP alone (arm B). Pelvic LN were dissected for qrt-PCR analysis, together with right and left lateral SM.
64,3% patients of arm B and 26.6% of arm A had evidence of PSA mRNA expression in LN and/or SM. 17,2% patients, all of arm B, had biochemical recurrence.
Qrt-PCR may be more sensitive, compared to conventional histology, in identifying presence of viable prostate carcinoma cells in SM and LN. Gene expression of PSA in surgical periprostatic samples might be considered as a novel and reliable indicator of minimal residual disease after NT.
Journal of Translational Medicine 05/2004; 2(1):13. DOI:10.1186/1479-5876-2-13 · 3.93 Impact Factor
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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.
Oncology Reports 05/2002; 9(3):545-9. DOI:10.3892/or.9.3.545 · 2.30 Impact Factor
Available from: Mark R Wick
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ABSTRACT: Virtually all anatomic pathologists are involved in the assessment of tissue margins in surgical procedures that are performed for malignant diseases. The natural tendency to view this process as uncomplicated has, in recent years, been countered by a body of literature on the biological milieu of the marginal zone. Moreover, empirical clinical information has shown that "negative" and "positive" marginal status has an imperfect correlation with risk of recurrent disease in several organ systems and in reference to various tumor types. Problems also remain regarding the optimal techniques for pathologic sampling of margins; the possible roles, if any, of adjuvant (eg, immunohistologic and "molecular") procedures for margin evaluation, and reporting motifs for selected surgical resections. This review considers conceptual data now available on surgical margins, provides a working approach to the generic assessment of marginal surfaces, and presents organ- and tumor- specific information pertaining to this area of practice.
Seminars in Diagnostic Pathology 12/2002; 19(4):207-18. · 2.56 Impact Factor
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