Expression of bcl‐2 and p53 oncoproteins in schistosomiasis‐associated transitional and squamous cell carcinoma of urinary bladder

OBJECTIVES: To analyze the expression of bcl-2 and p53 proteins in schistosomiasis-associated bladder cancer compared to adjacent urothelium showing morphological alteration including hyperplasia, metaplasia and dysplasia. MATERIALS AND METHODS: Twenty-two formalin-fixed and paraffin-embedded samples of histologically confirmed schistosomiasis-associated bladder tumours were assessed for grade, pathological stage (pT category) and the presence of hyperplasia, metaplasia and dysplasia in adjacent mucosa. There were 11 transitional cell carcinomas (TCCs), 10 squamous cell carcinomas (SCCs) and one diffuse infiltrating (signet-ring cell type) adenocarcinoma. Epithelial hyperplasia was observed in seven cases and metaplasia in 18, most of which were squamous except for a single case of glandular metaplasia. Focal dysplastic areas were observed in eight cases. Sections were stained immunohistochemically for the expression of bcl-2 and p53 proteins. RESULTS: Immunoreactivity for bcl-2 was present in seven of 22 cases (four SCCs and three TCCs) of which three cases (two SCCs and one TCC) were strongly positive, but in contrast to previous studies, there was no increase in the poorly differentiated tumours, bcl-2 was absent in metaplastic and dysplastic epithelium (except in a single case of glandular metaplasia) but it was present at low levels in basal cells of morphologically normal or hyperplastic transitional epithelium in 15 of 22 cases. Nine of 11 TCCs and seven of 10 SCCs showed p53 nuclear immunoreactivity. Heterogenous weak to moderate immunoreactivity for p53 was seen in 13 of 18 cases of metaplasia and in seven of eight cases of dysplasia in the mucosa adjacent to tumours, p53 was absent in normal and hyperplastic urothelium. Co-expression of p53 and bcl-2 was only seen in well differentiated areas of three tumours (two SCCs and one TCC). CONCLUSION: This study detected the expression of bcl-2 in a subset of bladder cancers (32%), whereas most (72%) of the tumours expressed immunoreactive p53. Additionally, p53 was also detected in metaplastic and dysplastic epithelium. Over-expression of both p53 and bcl-2 in the same tumour was only evident in a minority of schistosomiasis-associated cancers (13%). There was no inverse relationship of p53 and bcl-2 immunoreactivity.