P53 codon 72 (Arg72Pro) polymorphism and prostate cancer risk: association between disease onset and proline genotype.

The tumor suppressor gene p53 plays an important role in the stress response of the cell and is mutated in 50% of all human tumors. The p53 Arg72Pro single-nucleotide polymorphism (SNP) was found to be associated with an increased risk of various malignancies. Biochemical and biological differences between the 2 polymorphic variants of wild-type P53 might lead to distinct susceptibility to HPV- and non-HPV-induced tumors. For prostate cancer, only limited data are available, especially in the Caucasian population. Therefore, we determined the distribution of the Arg72Pro SNP in a Caucasian case-control study including 118 prostate cancer patients and 194 male controls without any malignancy using restriction fragment length polymorphism analysis. A subset of 33 tumors was tested for HPV infection, and no HPV DNA was found. Cases and controls showed similar distributions of alleles in the SNP (p = 0.720). Regarding the onset of the disease, patients diagnosed at ≤60 years of age and older patients (>60 years of age) showed a significant difference in genotype distribution (p = 0.035); there was also an increased occurrence of risk allele Pro72 in cases aged ≤60 years (p = 0.045). A subset of 64 prostate tumors was stained immunohistochemically for P53. 5 of 64 prostate tumors (7.8%) were positive for P53 expression, indicating integrity of the protein in the majority of cases. Genotype distribution showed no association with the Gleason score or additional histopathological characteristics. This study shows that the overall risk of prostate cancer was not associated with Arg72Pro SNP and HPV infection in our cohort. However, disease onset might be modulated by the p53 Pro72 allele, suggesting an important role of apoptosis regulation in prostate carcinogenesis.

Mutational activation of FGFR3 is not involved in the development of prostate cancer.

OBJECTIVE: The mutational constitutive activation of FGFR3 has been discovered in several malignancies but only limited data on FGFR3 mutations in prostate cancer are available. Most recently, activating FGFR3 mutations were described as being associated with low-grade prostate tumors. Therefore, we investigated the FGFR3 mutation status in a comprehensive series of prostate tumors. METHODS: 102 archival formalin-fixed paraffin-embedded prostate tumors of patients treated with radical prostatectomy [with a low-grade subgroup (Gleason score ≤6) of 29 patients] as well as 29 incidental prostate tumors [low-grade tumors (Gleason score ≤6); n = 22] and 16 benign prostatic hyperplasia samples obtained by transurethral resection of the prostate were investigated. After microdissection and DNA isolation, all FGFR3 mutation hotspots discovered in human malignancies were analyzed using the SNaPshot(©) approach or restriction fragment length polymorphism (RFLP) analysis. RESULTS: All cases could successfully be analyzed by SNaPshot; 80 cases were investigated using RFLP. No mutation in FGFR3 could be detected in any of the analyzed cases. CONCLUSION: The most recently reported FGFR3 mutations in low-grade prostate tumors could not be verified in our series. There were also no mutations in prostate tumors from patients with concomitant bladder tumors as reported previously. These data suggest that the mutational activation of FGFR3 plays no important role in prostate carcinogenesis, which is in accordance with previous studies performed on smaller tumor cohorts.

Eight years' experience with high-intensity focused ultrasonography for treatment of localized prostate cancer.

OBJECTIVES: To report on the long-term results of high-intensity focused ultrasonography (HIFU) in the treatment of localized prostate cancer. METHODS: Patients with clinical Stage T1-T2N0M0, biopsy-proven, localized prostate cancer, with a serum prostate-specific antigen (PSA) level of

Factors predicting for formation of bladder outlet obstruction after high-intensity focused ultrasound in treatment of localized prostate cancer.

OBJECTIVES: To assess the potential factors influencing the occurrence of bladder outlet obstruction (BOO) during follow-up after high-intensity focused ultrasound (HIFU) treatment for localized prostate cancer. METHODS: Patients treated with HIFU who had a minimal follow-up of 1 year were included in this retrospective analysis. BOO was classified as bladder neck, necrosis of the prostate, distal stenosis, urethral stenosis, and single and repetitive BOO. We analyzed the risk group (American Joint Commission on Cancer), age, prostate volume before HIFU, treated prostate volume on HIFU, pre-HIFU transurethral resection of the prostate (TURP), ratio of resected volume/initial prostate volume by TURP before HIFU, and interval between TURP and HIFU. P values of less than 0.05 were considered statistically significant. RESULTS: The mean follow-up of the 315 patients analyzed was 40 +/- 19 months (range 12 to 109). BOO developed in 79 patients (25.1%), with 19 experiencing multiple BOO episodes. The mean interval to the first development of BOO was 15.2 +/- 19.3 months. The distribution of a single episode of BOO for the etiologies of bladder neck, necrosis of the prostate, distal stenosis, and urethral stenosis was 64 (81%), 24 (30.4%), 13 (16.5%), and 10 (12.7%), respectively. Older age at HIFU was the only factor significantly associated with the development of BOO (P = 0.021). In those with multiple BOO episodes, the main type of obstruction was at the bladder neck. The rate of multiple BOO episodes was significantly lower with a greater volume of resected tissue by TURP before HIFU (P = 0.031). CONCLUSIONS: The results of our study have shown that the development of BOO after HIFU is associated with older age. TURP before HIFU was not an independent factor in the prevention of BOO during follow-up, but multiple BOO episodes were reduced by resecting more tissue at TURP before HIFU.

PSA nadir is a significant predictor of treatment failure after high-intensity focussed ultrasound (HIFU) treatment of localised prostate cancer.

OBJECTIVES: To assess if prostate-specific antigen (PSA) nadir is an independent predictor of treatment failure and disease-free survival after high-intensity focussed ultrasound (HIFU) therapy for localised prostate cancer as defined by the new ASTRO criteria. METHODS: One hundred three patients after HIFU treatment (Ablatherm, EDAP, Lyon, France) for localised prostate cancer without previous hormonal therapy were evaluated retrospectively. Patients attended regular follow-up visits every 3 mo. Treatment failure was defined by the revised ASTRO criteria (PSA >or=2 ng/ml above nadir PSA, positive biopsy, if salvage treatment was administered). Patients were divided into three PSA nadir subgroups (group 1, 1 ng/ml). The disease-free survival rate (DFSR) was calculated by using life table methods. The log-rank test was used to compare the curves based on Kaplan-Meier models. RESULTS: The median follow-up was 4.9 (3-8.6) yr. Mean time to PSA nadir was 6.4+/-5.1 mo. A PSA nadir of 1ng/ml was reached by 64%, 22.3%, and 13.6% of patients, respectively. Treatment failure rates during follow-up were 4.5%, 30.4%, and 100%, respectively, for the three groups (p<0.001). The actuarial DFSRs at 5 yr were 95%, 55%, and 0%, respectively, for the 3 groups (p<0.001). CONCLUSIONS: The PSA nadir after HIFU correlates highly significantly with treatment failure and DFSR, and can be applied in daily clinical practice. Promising oncological outcome is obtained if a PSA nadir of