HSP90 expression: a new predictive factor for BCG response in stage Ta-T1 grade 3 bladder tumours

Abstract

Objectives: Although Bacillus Calmette-Guérin (BCG) instillations are considered as the adjuvant treatment of choice for stage Ta-T1 grade G3 bladder tumours, there is no consensus for a predictive factor to assess BCG success. This study attempted to evaluate if heat shock proteins (HSPs) could be useful predictive markers in BCG responses.

Methods: Thirty-three primary resected G3 superficial bladder tumours were included in the study. All patients received adjuvant BCG instillations. The mean follow-up was 56 mo (range: 24-132 mo). HSP expression was evaluated by immunochemistry.

Results: In the 33 patients, 18 had no recurrence (group 1), 9 had recurrence with no muscular invasion (group 2), and 6 had an invasive recurrence (group 3). A significant correlation was found between lack of expression of HSP90 and BCG response: the mean HSP expression was 92.7%, 84.4%, and 26.7% for groups 1, 2 and 3 tumours, respectively (p<0.0001). For the 6 patients who did not positively respond to BCG, HSP expression was <40%. All the tumours with a HSP90 expression >40% positively responded to BCG, corresponding to group 1 or 2 patients. In contrast, HSP60 expression was not correlated to the BCG response.

Conclusions: HSP90 could be considered as a very promising marker to assess BCG treatment response. Low HSP90 expression (<40%) could be useful to predict BCG failure and early stage cystectomy could be proposed for these selected patients with primary high-risk grade 3 superficial bladder tumours.