The majority of patients with bladder cancer are initially diagnosed with noninvasive or superficially invasive urothelial tumors. These tumors form a heterogeneous group, spanning from benign low grade Ta tumors that rarely progress to high grade T1 tumors with concomitant CIS that progress in up to 60% of cases. No biomarkers have yet been accepted in clinical routine for predicting the individual disease courses of these patients. Previously, we have identified gene expression signatures for prediction disease outcome for patients with non-muscle invasive bladder cancer. The aim of the present study was to validate key candidate markers from these signatures on the protein level. Five genes were selected for investigation: CTSE, BIRC5, TRIM29, PLK1 and SERPINB5.

A total of 289 primary non-muscle invasive urothelial tumors (182 pTa, 101 pT1 and 6 CIS) were chosen for tissue microarray construction. 118 patients showed later disease progression to pT2-4 bladder cancer with a median time to progression of 22 months. None of the remaining 171 patients showed later disease progression within the follow-up period with a median follow-up of 93 months. Protein expression was investigated using immunohistochemistry.

We found that high expression of BIRC5 and PLK1 identified patients with an increased risk of progression; (HR=2.47 (1.57-3.87), P<0.001 and HR=1.52 (1.00-2.29), P=0.048 respectively). Whereas high expression of CTSE, SERPINB5 and TRIM29 identified patients with a reduced risk of progression; (HR=0.60 (0.39-0.93), P=0.02), (HR=0.58 (0.38-0.89), P=0.01) and (HR=0.38 (0.20-0.73), P=0.003 respectively).

We found all five proteins to be independent prognostic variables for predicting disease progression to muscle invasive bladder cancer when stratifying for other known clinical and histopathological risk factors. Consequently, we successfully transferred key markers from the gene expression signatures to the protein level. This marker panel is currently being validated in a new series of pT1 bladder tumors and the results from this independent validation set will also be presented at the meeting.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4642.