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Egypt. J. Exp. Biol. (Zoo.). 2012; 8(1): 145-153


MUTATION ANALYSIS AND EXPRESSION OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 IN BILHARZIAL URINARY BLADDER CARCINOMAS FROM EGYPTIAN PATIENTS

Elsayed I. Salim.




Abstract

Fibroblast growth factor receptor 3 (FGFR3) belongs to a family of structurally related tyrosine kinase receptors, the FGFR family, which regulate cell proliferation, differentiation, migration and angiogenesis. The present study aimed to analyze the possible prognostic value of FGFR3 gene in urinary bladder carcinomas from Egyptian patients infected with Schistosomia hematobium. The quantitative analysis of FGFR3 protein expression by immunohistochemistry showed significant overexpression in squamous cell carcinomas (SCCs) and low-grade non-invasive urothelial carcinomas (UCs) than in the high-grade invasive UCs. Further, the incidence of FGFR3 mutations, evaluated by PCR-single-strand conformation polymorphism (PCR-SSCP) technique and direct sequencing, were found in 6 out of 17 (35.3%) of SCCs histologically confirmed as pT2, pT3a or pT3b stages, and G2 or G3 grades. All SCCs had G→A base transitions in exon 7. Also 5 out of 10 tumors (50%) of non-invasive UCs of low grades (stages: pTa and pT1; grades: G1, G2) had mutations of G→A and T→C transitions in exons 10 and 15, respectively. In addition, one out of four (25%) invasive UC histologically confirmed as pT4 and G3, had mutations of A→G transition in exon 15. In conclusion, the results show that both SCCs either with high grades or low-grade papillary UCs have higher FGFR3 mutation and protein expression levels than high-grade invasive UCs in urinary bladder carcinomas from Egyptian patients with prior schistosomaisis.

Key words: Urinary bladder, Urothelial carcinomas, Squamous cell carcinomas, Schistosoma, FGFR3, Mutation, PCR-SSCP






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