Incidence of fibroblast growth factor receptor 3 gene (FGFR3) A248C, S249C, G372C, and T375C mutations in bladder cancer.

Bladder cancer is the most frequent cancer of the urinary system. Fibroblast growth factor receptors (FGFR) belong to the tyrosine kinase family and have important roles in cell differentiation and proliferation and embryogenesis. FGFR3 is located on chromosome 4p16.3, and missense mutations of FGFR3 are associated with autosomal dominant human skeletal disorders and have some oncogenic effects. We examined the incidence of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, and their correlation with clinical-pathological parameters in bladder carcinoma patients. Fifty-six paraffin-embedded specimens of transitional cell carcinoma of the urinary bladder were included in this study. Analysis of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, was performed by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, were detected in 33 of the 56 patients (heterozygous mutant). Among the 56 transitional cell carcinomas, missense point mutations were detected in seven of them at codon A248C, 28 of them at codon S249C, and three of them at codon T375C, similar to data from previous reports. When the results of the FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C and in exon 10, G372C and T375C, were analyzed one by one or as a group, despite the findings of previous research reports, our data suggest that these mutations are detected homogenously regardless of the tumor classification and tumor grade.

The effect of the sun on expression of beta-catenin, p16 and cyclin d1 proteins in melanocytic lesions.

BACKGROUND: The tumour suppressor gene product, p16, is often inactivated during melanoma malignant progression. Although the importance of p16 in melanomas is well documented, its relationship with cyclin D1, beta-catenin and ultraviolet radiation (UVR) remains unclear. AIM: To determine the role of these cell cycle-related proteins and high-risk sun exposure in the biological behaviour of melanocytic lesions. METHODS: We used immunohistochemistry to examine 28 melanocytic naevi (MN; 9 congenital and 19 acquired types) and 24 primary cutaneous malignant melanomas (CMM; 19 nodular melanomas, 3 lentigo maligna melanomas, 1 acral lentiginous melanoma and 1 superficial spreading melanoma) for the presence of p16, cyclin D1 and beta-catenin. The melanocytic lesions were classified into two groups to examine the effects of UVR on these three proteins: high risk of sun exposure (chronically sun damaged; CSD), or low risk of sun exposure (nonchronically sun damaged; non-CSD). We evaluated the relationship between the production of these proteins and the histopathological and clinical characteristics of the lesions. RESULTS: Production of p16 was repressed in most CMM, but not in MN (P < 0.0001). Cyclin D1 was overproduced in CMM but not in MN, and beta-catenin was frequently overproduced both in MN and CMM. Overproduction of beta-catenin was not common in CSD melanocytic lesions, but was more frequent in non-CSD melanocytic lesions (P = 0.027). CONCLUSION: An immunohistochemical panel including melanocytic markers enriched by p16 and cyclin D1 could be used to differentiate some borderline melanocytic lesions. In addition, the Wnt/beta-catenin pathway was more frequently activated in non-CSD than in CSD melanocytic lesions.