TP53 Mutation in Prostate Needle Biopsies - Comparison with Patients Follow-up

Abstract

Background: The predictive value of TP53 mutations and prostate-specific antigen (PSA) was assessed in prostate needle biopsies of samples without signs of malignancy for later affliction by prostate cancer (PCa). Comparison of mutation frequency and PSA level in prostate needle biopsies with data of patients with benign prostate hyperplasia (BPH) treated by transurethral resection (TURP), patients with prostatic intraepithelial neoplasia (PIN), and patients with PCa, was made. Materials and Methods: A total of 466 samples were analysed from patients with benign and malignant diseases of the prostate, including 52 samples of needle biopsies of the prostate with repeated benign histopathological diagnosis. Analysis of TP53 state by temperature gradient gel electrophoresis of TP53 exon-specific PCR products of exons 5, 6, 7 and 8 was peformed. Clinical follow-up of 100 patients with benign diseases of the prostate and with PIN was available. Results: Needle biopsy samples with repeated benign diagnosis resemble BPH specimens taken by TURP in TP53 mutation frequency (TURP: 16.1%, needle biopsy: 21.2%) and later affliction by PCa (TURP: 3/32 =9.4%, needle biopsy: 8/51 = 15.7%, p=0.409). Patients with TP53 mutations in needle biopsy samples showed a significantly reduced disease-free survival time for affliction by PCa (log rank: p=0.0149). This significance is raised by computing exon 6 mutations only with respect to affection by PCa (p=0.0002). In TURP patients, exon 7-mutations were also significant (p=0.0086). Needle biopsy TP53 mutations (p=0.029) had significant predictive values for later affliction by PCa in multivariate analysis. PSA level and patient age had no predictive value for PCa. Conclusion: TP53 mutations reduce the PCa-free survival time in patients with needle biopsy of the prostate and primary benign diagnosis. Exon 6 mutations enhance the risk of being affected by PCa 32-fold.