Evaluation of cellular transformation and tumor aggressiveness factor expression in urinary bladder lesions and transitional cell carcinoma special variants in relation to bilharziasis

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Abstract

Background

Identification of molecular factors as diagnostic and prognostic indicators, as well as targets, for better therapy is a high priority. Human epidermal receptors constitute a family of receptor tyrosine kinases, which appear to be implicated in cellular transformation and can be overexpressed in a variety of solid tumors. Moreover, there has been a progressive interest in the expression of CD44 as a marker of tumor aggressiveness and metastatic potential in some human cancers.

Hypothesis

A variety of urinary bladder lesions and urothelial neoplasms are associated with alterations in epithelial growth factor receptor (EGFR) and CD44 gene and protein expression. Studying these factors using immunohistochemical methods and selectively using fluorescent in-situ hybridization (FISH) technique may give an idea of the influence of bilharziasis upon induction and progression of these lesions.

Patients and methods

Biopsies from 150 patients with urinary bladder lesions were subjected to histopathological examination, immunohistochemical detection of EEGF and CD44, and gene expression of EGFR using the FISH technique.

Results

Malignant urothelial lesions showed a higher percentage of cellular positivity and scores for both markers compared with control and cystitis cases (P<0.01). Cases of bilharzial cystitis showed significantly higher percentages and higher scores of CD44 expression compared with nonbilharzial cystitis cases (P<0.01). Bilharzial [transitional cell carcinoma (TCC)+squamous cell carcinoma (SCC)] cases showed significantly higher scores of both EGFR and CD44 expression, compared with nonbilharzial (TCC+SCC) cases. EGFR protein and gene were upregulated in malignant urothelial lesions – namely, TCC and SCC – with significant correlation with grade of neoplasia. CD44 expression was also upregulated in urothelial bladder lesions, especially SCC, and was correlated positively with both the grade and the stage of malignancy. All examined control, cystitis, and adenocarcinoma cases showed negative results for EGFR gene activation using FISH technique. All cases of bilharzial TCC showed positive gene expression, which is considered significant when compared with other nonbilharzial TCC (P<0.01). No significant difference in gene expression was detected between bilharzial and nonbilharzial cases of SCC (P>0.05).

Conclusion

In our study we found that grouping cases of TCC+SCC showed significantly higher scores for both EGFR and CD44 expression in bilharzial patients compared with nonbilharzial patients, pointing to the possible role of bilharzial infection in progression of cancer. TCC subgroups, although small in number, showed variable expression of EGFR and CD44, denoting possibly different molecular backgrounds. FISH results confirmed EGFR upregulation in TCC and SCC but not in adenocarcinoma.

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