Objectives: To identify and analyse point mutations in p53 tumour suppressor gene (Tp53) in benign prostatic hyperplasia (BPH) by temperature gradient gel electrophoresis (TGGE) and sequence.
Materials and methods: 141 tissue specimens (approx. 100 mg) after transurethral resection of the prostate (TURP), 12 specimens after needle biopsy. Control samples for genetic analysis were (a) 7 prostate tissues without any sign of BPH and malignancy and (b) 103 prostate cancer (PCa) tissues. DNA of the critical Tp53 exons 5-8 was amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done from re-amplified mutant and wild-type bands.
Results: TGGE screening of 153 BPH samples identified 29 specimens with Tp53 mutations (5 in exon 5, 11 in exon 6, 12 in exon 7, 3 in exon 8; 1 tissue sample showed mutations in 3 exons at a time). The computed mutation frequency was 19.0%. Two patients, with mutation in BPH tissue, developed PCa 2-3 years after TURP. One patient with mutation in BPH tissue developed bladder cancer. Of 118 patients with non-mutated DNA in BPH, none is known to have a urological cancer. The Tp53 mutation frequency in 103 PCa samples was 26.2%. Significant differences of mutation frequency between BPH and PCa were detected only in lower exon 5 mutation counts in BPH.
Conclusion: Tp53 mutation in BPH tissue may be a tumour risk factor.