The Relationship Between Catechol Oestrogen and Bladder Pathologies in Human Urinary Schistosomiasis

Abstract

Bladder pathologies associated with urinary schistosomiasis begin in the subepithelial tissues before invading the epithelial tissues. Urine cytopathology although specific with an added advantage of non-invasive sampling, has a limitation because subepithelial bladder pathologies cannot be picked up. They do not exfoliate into the urine that is used for diagnosis or screening. Schistosoma haematobium egg antigen contains catechol oestrogen (CE) which is categorized as a class I carcinogen and soluble in urine. Archived bladder biopsies from the Department of Pathology, University of Ghana Medical School and urine samples from two S. haematobium endemic communities (Zenu and Weija) were used for the study. Both the community urine samples and archived tissue samples were analysed for the presence of S. haematobium ova using wet preparation and Haematoxylin and Eosin staining technique respectively. Again, smears were prepared from urine sediment, wet fixed and stained with Papanicoulaou staining technique for diagnosis of bladder pathologies by cytology. Tissue sections prepared from archived biopsies were stained with Haematoxylin and Eosin (H & E) for diagnosis of bladder pathologies by histopathology. Concentration of CE in urine was estimated using ELISA technique whilst immunocytochemistry was used to demonstrate biomarkers Ki67, cyclin D1 and HER2. Analysis of community samples showed that participants aged from 6-19 were 1.76 times more likely to have bladder pathologies with reference to those above 60 (OR=1.76, (95%CI; 1.039, 2.982) p=0.017) whereas males were 41% less likely to develop bladder pathologies than females (OR=0.410, (95%CI: 0.204, 0.825) P=0.0124). There was significant association between squamous cell carcinoma and the presence of S. haematobium (χ2=56.738, p<0.001). Patients diagnosed with squamous cell carcinoma were 6.8 times more likely to test positive for S. haematobium infection compared to those patients who tested negative [OR = 6.833, (96% CI: 3.944 to 11.839) p<0.001]. A highly significant correlation existed between ova counts and CE concentration in urine (r=0.4218, 95% CI: 0.3379 to 0.4991, p<0.001). Significant differences in CE concentration were also observed among the categories of bladder pathologies (p< 0.001). Using urine samples, the Receiver Operating Characteristic (ROC) curves show that CE has an excellent predictive ability to discriminate bladder pathology patients from normal individuals and more sensitive than the other molecular markers such as Ki67, cyclin D1 and HER2. This study found a strong statistical correlation between some bladder pathologies (squamous cell carcinoma, urothelial dysplasia squamous metaplasia) and schistosomiasis infection. High concentration of CE was associated with S. haematobium infection and abnormally high expression of Ki67 is expressed in bladder pathology in endemic areas