Impact of density of schistosomal antigen expression in urinary bladder tissue on the stratification, cell type, and staging, and prognosis of carcinoma of the bladder in Egyptian patients

Abstract

BackgroundInfection with urinary schistosomiasis and its severity are oncogenic factors for developing carcinoma of the bladder, whether it is urothelial carcinoma (UC) of a transitional cell type (TCC) or non-urothelial of squamous cell carcinoma (SCC). In UC it is not defined whether it is schistosomal or not. This led to controversial results in expression of tumour markers, tumour prognosis, and response to therapy.ObjectivesWe assessed the application by immunohistochemistry method (IHC) for detection of schistosomal antigen in bladder cancer tissue samples to differentiate UC associated with or without schistosomiasis. Urothelial carcinoma stage, grade, and progression were correlated with the density, intensity, and index of schistosomal antigen expression. Follow up was done for 2-5 years.Design and participantsArchival tissue samples of 575 patients were studied: 515 urothelial carcinoma, 30 patients with SCC associated with schistosomiasis, and a control group of 30 patients without schistosomiasis.MeasurementsExpression of schistosomal antigen in tissue was done by IHC using monoclonal antibodies (MAbs) against schistosomal antigens (SA). Correlation of intensity of antigen expression to clinical and pathological data was analysed.Results and limitationsWe identified 3 parameters of antigen expression: density, intensity and index with 4 grades for each. SCC-group was 100% positive. UC was positive in 61.4% distributed as follows: Ta: 37.5%, T1: 62%, and muscle invasive T2-4 were 64%. Upstaging, metastases and recurrence were correlated with high index in T1 and T2-4 tumours.ConclusionUrothelial carcinoma associated with schistosomiasis was defined by the positive expression of schistosomal antigens in tissues detected by lHC using MAbs against schistosomal haematobium. Upstaging and progression of T1 and T2-4 were correlated with high density, intensity, and index of antigen expression. Non-schistosomal UC had negative expression for schistosomal antigen, which was detected in 36.5% of cases. These results would be of significance in differentiating schistosomal from non-schistosomal bladder cancer of UC and would predict the prognosis in T1, T2-3 tumours. Implementation of IHC using MAbs against SA in UC would help in planning the proper therapy. Schistosomiasis should be considered as an oncogene for UC in endemic areas.

Schistosomiasis and Bladder Cancer in Egypt: Truths and Myths

“…-The studies on the molecular basis of bladder cancer in Egypt and its changing patterns are limited [44], [45], [46], [47], [48], [49], [50].…”

Neglected Agent Eminent Disease: Linking Human Helminthic Infection, Inflammation, and Malignancy

“…These metabolites are known for their carcinogenic properties. The chronic inflammation marks the onset of the disease schistosomiasis, which increases risk of urothelial hyperplasia, dysplasia, and SCC (Parkin, 2006; Wishahi et al, 2014). The infection can be acute, with symptoms like headache, fever, fatigue, abdominal pain, etc.…”

Elevated Levels of Urinary 8-oxodG Correlate with Persistent Periductal Fibrosis after Praziquantel Treatment in Chronic Opisthorchiasis

“…22 Similar findings for the presence of parasite antigen in the body tissue have been reported in Schistosoma haematobium-associated urothelial carcinoma inflammation and cancer tissues. 23 Second, persistent biliary fibrosis may be driven by a pro-inflammatory cytokine, interleukin-6 (IL-6), released from the fibrotic tissue. 24 A previous study revealed that the level of IL-6 was eight times higher in human opisthorchiasis with advanced PDF than those without advanced PDF.…”