VAIL, CO USA (UroToday.com) - A 63-year old male with history of persistently increased serum levels of prostate specific antigen (PSA) over the past five years and five transrectal ultrasound-guided (TRUS) biopsies negative for malignancy.
Magnetic Resonance Imaging of the prostate revealed no definite evidence for prostate cancer (PCa). PCA3-test (a molecular assay that detects the presence of the PCa-associated transcript in urine after prostate massage) had a score of 18 at time of admission, suggesting a decreased probability for a positive repeat biopsy. Transperineal mapping biopsies (TPMB) were performed as the most appropriate procedure to follow. From ninety-nine biopsy samples, nine (10%) were found positive for PCa and located bilaterally at the anterior aspect of the prostate. The patient chose to have a prostatectomy from which he has fully recovered. A dynamic 3-dimensional (3D) image of the prostate was constructed showing the location of the PCa lesions. These 3D images were then correlated with the pathology results of the whole mount prostatectomy specimen, which was processed completely. The location of these lesions correlated very well with the PCa location observed in the 3D reconstruction of the TPMB.
A blinded epigenetic profile (ConfirmMDx test for PCa by MDxHealth, Irvine, CA) of the TPMB samples was performed to detect DNA methylation of the genes GSTP1, APC and RASSF1. A comparative analysis between the histological results of the TPMB and their epigenetic profile revealed an excellent molecular and histopathologic correlation. The epigenetic profile also identified two RASSF1 positive foci located at the posterior aspect of the prostate, in which no PCa was identified. Pathology re-examination of the whole mount prostatectomy sections revealed in these areas two small foci of high-grade prostatic intraepithelial neoplasia (HG-PIN) admixed with a few atypical small acinar proliferations (ASAP), which were confirmed by a double immunostaining for p63 and racemase.
In this relatively unusual case study, occult PCa was eventually detected and properly treated with the practice of a multidisciplinary approach. TPMB was successfully used to identify clinically significant cancer, as high as Gleason score (GS) 9, which was missed by 5 prior TRUS biopsies. The epigenetic assay was able to correctly identify all significant PCa lesions recognized by histopathology in the TPMB. Two additional positive methylation foci for the RASSF1 gene led to a second histopathology review of the whole mount prostatectomy sections with the finding of two areas of previously overlooked HG- PIN and ASAP. The coordinated use of TPMB and epigenetic tests could also be used to generate useful information for patient prognosis. Such assays could eventually provide objective parameters for patient management and the use of molecular oriented therapy. Currently, GS is the main prognostic factor determining the aggressiveness of PCa; however, scoring discrepancies between pathologists and between biopsies versus prostatectomy specimens usually provide inconsistent information about specific risk factors and clinical outcomes. In addition, GS becomes less reliable because TRUS biopsies suffer from inherent sampling errors. In the future epigenetic assays could overcome these limitations and might provide more useful information regarding disease aggressiveness and clinical outcome.
Presented by Francisco G. La Rosa, MD, Cliff Jones, DDS, Paul Arangua, E. David Crawford, MD, and Leander Van Neste, PhD at the 24th International Prostate Cancer Update - February 19 - 22, 2014 - Cascade Conference Center - Vail, Colorado USA
University of Colorado, Anschutz Medical Campus, School of Medicine, Department of Pathology,
University of Colorado Cancer Center and University of Colorado Hospital