Abstract
Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.
Highlights
Urinary bladder carcinoma (UBC) is the first ranking tumor in Egyptian males and it represents 34.26% of male malignant tumors; it is characterized by high frequency of squamous cell carcinoma (SCC) due to Schistosomiasis which induces squamous metaplasia of the urothelium (Mokhtar et al, 2007)
The proto-oncogene c-KIT encodes a 145-160 kDa, type III transmembrane tyrosine kinase receptor known as c-KIT or CD117 (Vliagoftis et al, 1997; Tian et al, 1999), which belongs to the same family of receptors as platelet-derived growth factor and colony-stimulating factor (Yarden et al, 1987; Vliagoftis et al, 1997)
In terms of therapeutic strategies, it has become important to evaluate the frequency of c-KIT expression and mutation in malignancies since the emergence of the targets of the tyrosine kinase inhibitor imatinib mesylate (STI571; Gleevec;) a potential therapeutic agent which inhibits the action of BCL-ABL in chronic myeloid leukemia and c-KIT in gastrointestinal stromal tumor
Summary
Urinary bladder carcinoma (UBC) is the first ranking tumor in Egyptian males and it represents 34.26% of male malignant tumors; it is characterized by high frequency of SCCs due to Schistosomiasis which induces squamous metaplasia of the urothelium (Mokhtar et al, 2007). Binding of SLF to KIT results in receptor homodimerization, activation of KIT tyrosine kinase activity, and resultant phosphorylation of a variety of substrates. In terms of therapeutic strategies, it has become important to evaluate the frequency of c-KIT expression and mutation in malignancies since the emergence of the targets of the tyrosine kinase inhibitor imatinib mesylate (STI571; Gleevec;) a potential therapeutic agent which inhibits the action of BCL-ABL in chronic myeloid leukemia and c-KIT in gastrointestinal stromal tumor. We investigated the expression and mutation frequency of c-KIT in urinary bladder SCCs from Egyptian patients and its relation with Schistosomiasis and various clinicopathologic variables, since this could provide us with useful information concerning whether the drud Imatinib mesylate might be effective against this aggressive malignancy. Imatinib mesylate acts by inhibiting tyrosine kinase receptor that is characteristic of a particular cancer cell, rather than nonspecifically inhibiting and killing all rapidly dividing cells (Gambacorti-Passerini, 2008)
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