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Abstract
Purpose: Bladder cancer is the fourth most commonly diagnosed malignancy in men and ninth most commonly diagnosed malignancy in women. At initial presentation, between 70 to 80% of tumours are categorised as superficial papillary urothelial carcinoma (UC). Between 55-90% of these low grade tumours will recur within 5 years, and while less than 5% will become invasive or lead to mortality, currently it is not possible to determine between those patients likely to develop progressive disease and those who do not.
Nucleoside analogues, such as gemcitabine, provide a novel treatment approach for superficial UC. While the direct and indirect mechanisms by which gemcitabine enters and affects tumour cells are moderately well understood in organs such as pancreas, they are still unknown in UC. This project undertook to examine relevant biomarkers (hENT1 (SLC29A1), p53, EGFR and Her-2) in UC and normal bladder epithelia and discover whether potential relationships existed between these biomarkers, gemcitabine clinical response and patient characteristics such as age, gender and grade.
Method: A retrospective study was conducted on bladder tissue from 2 patient cohorts (total of 80 patients). The first cohort consisted of patients participating in a multicentre Phase II trial of intravesical gemcitabine for recurrent superficial UC. The second cohort were participants of a longitudinal study of the aging bladder, with no urological pathological disease. A series of immunohistochemistry studies for the biomarkers hENT1, p53, EGFR and Her-2 were performed with a novel immunohistochemistry stain was successfully developed for the research antibody hENT1 on formalin fixed, paraffin embedded, bladder urothelia.
Result: The expression of hENT1, Her-2 and EGFR and their relationships to various patient characteristics was established for the first time in healthy urothelia. Expression of hENT1 in UC was also established for the first time. Statistical analysis found a direct relationship between p53 and patient gemcitabine response, but not with hENT1, EGFR and Her-2 immunohistochemistry scores.
Conclusion: Relationships were discovered between the selected biomarkers and various patient clinical characteristics including the possible prognostic ability of hENT1 regards UC recurrence however, no direct relationship between the selected biomarkers and gemcitabine response was detected was found.