Immunohistochemical expression of CD117/KIT, HER2, and Erβ in schistosomal and non-schistosomal urothelial carcinoma of Egyptian patients

Abstract

Bladder carcinoma is an endemic problem in Egypt with schistosomiasis being an additional risk factor. Due to gender disparities, Erβ investigation and its role in modulating chemosensitivity are studied. CD117/KIT expression is also considered since the emergence of the targets of the tyrosine kinase inhibitor imatinib mesylate (Gleevec). HER2 is one of the established therapeutic targets in many cancers. We aimed to investigate CD117/KIT immunoexpression in schistosomal and non-schistosomal urothelial carcinoma of Egyptian patients and its relationship with HER2 and Erβ expressions, correlating it with pertinent variables that will help to provide better treatment options of possible combined targeted and hormonal therapy that might be effective against this aggressive malignancy. Sixty cases of bladder carcinoma were tested. Depending on the schistosomiasis association status of each case, two groups have been established with 30 cases each. CD117/KIT, HER2, and ERβ immunostaining were done and correlated with clinico- immuno-pathological parameters. CD117/KIT expression was seen in 71.7% of cases that correlated significantly with schistosomiasis (P = 0.01). In addition, a positive correlation was detected between schistosomiasis association and the percentage of immunostained cells and intensity score of CD117/KIT with P = 0.027, 0.01, respectively. 30% and 61.7% of cases were positively stained with HER2 and Erβ, respectively, with no significant relation with schistosomiasis. Due to the high expression, we found further clinical trials are needed to offer individualized targeted therapeutic options in urothelial tumors using anti-CD117/KIT, HER2, and ERβ other than limited traditional chemo- and nontargeted therapies.

Keywords: CD117/KIT; ERβ; HER2; Schistosomiasis.

Fig. 1

A High-grade urothelial carcinoma, showing strong CD117/KIT cytoplasmic expression in more than 50% of tumor cells (original magnification, CD117/KIT, × 400). B Negative expression of CD117/KIT in urothelial carcinoma associated with schistosomiasis (original magnification, CD117/KIT, × 400)

Fig. 2

High-grade invasive urothelial carcinoma showing cytoplasmic and strong complete membrane staining for HER2 in more than 10% of tumor cells (original magnification, HER2, × 400)

Fig. 3

High-grade invasive urothelial carcinoma showing strong positive nuclear ERβ staining in more than 80% of the tumor cells (original magnification, ERβ, × 200)