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

Bladder carcinoma is an endemic problem in Egypt with schistosomiasis being an additional risk factor. Due to gender disparities, Erß 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 Erß 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 ERß 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 Erß, 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 ERß other than limited traditional chemo- and nontargeted therapies.

Causes of secondary non-alcoholic fatty liver disease in non-obese children below 10 years.

This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children < 10 years from hepatologist perspectives. Infants and children below 10 years of age with biopsy-proven fatty liver over a 6-year period were included. NAFLD activity score was used to detect the presence of non-alcoholic steatohepatitis (NASH). The study included 66 cases whose age ranged between 5 months and 10 years. Transaminases were elevated in 60% patients. Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). The cause of steatosis could not be identified in 28.8% of cases. There was a higher prevalence of secondary causes of NAFLD in patients < 10 years. Liver histopathological examination revealed preserved lobular architecture in 75.7% with minimal-to-mild fibrosis in 79%. Steatosis was macrovesicular in all specimens (severe steatosis in 39.4%). Four patients had NASH. Higher degree of steatosis was associated with more severe fibrosis (P = 0.01).Conclusion: GSD was the commonest cause of secondary NAFLD in Egyptian children < 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. The degree of fibrosis was significantly related to the degree of steatosis.What is Known:• Primary non-alcoholic fatty liver disease (NAFLD) is rare in children aged less than 10 years.• Secondary causes of NAFLD should be considered in patients who do not have traditional risk factors.What is New:• Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (< 10 years) with higher degrees of steatosis in younger patients.• The degree of liver fibrosis is significantly related to the degree of steatosis.

HER-2 Immunohistochemical Expression in Bone Sarcomas: A New Hope for Osteosarcoma Patients.

BACKGROUND: Osteosarcoma and chondrosarcoma, remain the most common primary bone tumours. Questions have been raised about the prognostic influence of HER-2 in bone sarcomas, but so far the results have been debatable. The her-2 expression is possibly a predictor of chemotherapy response. AIM: In this study, we investigated the extent of HER-2 expression in bone sarcomas, and attempted to correlate it with pertinent variables that will help to provide better treatment options, especially for metastatic ones. MATERIAL AND METHODS: Fifty-two cases of bone sarcomas (32 osteosarcoma cases and 20 chondrosarcoma ones) were studied for HER-2 immunohistochemical expression then correlation with all available clinicopathologic features was done. RESULTS: Most of the osteosarcoma cases exhibited membranous staining (78.1%). Strong staining was observed (score 3+) in 34.4%; while 21.9% showed moderate staining (score 2+); and 21.9% displayed weak staining (score 1+), on the other hand, no staining was detected in 7 out of 32 cases (21.9%) (score 0). As regards chondrosarcoma, the absence of staining in all examined cases was noted. Immunohistochemical HER-2 overexpression correlated significantly with osteosarcoma site with P value = 0.004, with variation relating HER-2 intensity score to the site of osteosarcoma (P = 0.051). A statistically significant negative correlation was detected between HER-2 expression and the presence of metastasis at time of diagnosis (P = 0.006), A significant correlation was also found regarding HER-2 score and presence of metastasis with P value = 0.046 as more than half of cases with no metastasis at diagnosis (17/28 cases, 60.7%) showed positive intensity score. A statistically significant correlation was detected between HER-2 expression and patients' age (P = 0.044). Also, HER-2 expression significantly correlated to histopathological detection of fibrous tissue, with P value = 0.033. Higher scores of HER-2 expression were associated with a significantly better differentiation (P = 0.038) since detection of wide areas of osteoid were associated with higher HER-2 scores. CONCLUSION: Further research would still be needed to delineate HER-2 role being a new hope for therapeutic targeting in bone sarcoma patients, mainly osteosarcoma in contrast to chondrosarcoma that didn't express HER-2 at all.