ABSTRACT
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.
Subject(s)
Genes, p53 , Polymorphism, Single Nucleotide , Prostatic Neoplasms/genetics , Adult , Age of Onset , Aged , Aged, 80 and over , Alleles , Amino Acid Substitution , Base Sequence , Case-Control Studies , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Papillomavirus Infections/complications , Polymorphism, Restriction Fragment Length , Prostatic Neoplasms/etiology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Risk Factors , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
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.
