T1 High Grade Bladder Carcinoma Outcome: The Role of P16, Topoisomerase-Ii Alpha, Survivin and E-Cadherin.

Abstract High grade papillary urothelial carcinoma with subepithelial connective tissue invasion (T1HG) is an aggressive disease at high risk of progression after transurethral resection/Bacillus Calmette-Guerin standardized therapy. The European Organization for Research and Treatment of Cancer has identified T1HG bladder carcinoma which are single and ≤3 cm in the largest dimension at first diagnosis as a category in which the prognosis cannot be further stratified based on conventional criteria. This category may benefit from biomarker analysis as a valuable tool to determine the patient's outcome. To further the issue of biomarkers in predicting aggressiveness in T1HG bladder carcinoma which were single and ≤3 cm in greatest dimension at first diagnosis, we have conducted a validation study of the biomarker risk score set previously reported by our group. The study set included imunohistochemical detection of Galectin-3, CD44, E-cadherin (E-CAD), CD138, p16, Survivin, HYAL-1, and topoisomerase-II alpha (TOPO-2α) in 92 randomly selected specimens at participating institutions. TOPO-2α expresssion was identified as a predictor of disease-free survival. P16, survivin and E-cadherin expression predicted progression-free survival, but p16 and E-CAD also predicted overall survival. The current study validates a panel of immunohistochemical markers with the potential of being implemented in practice, and supports the use of biomarkers in predicting aggressiveness in patients with first diagnosis of T1HG bladder carcinoma which were single and ≤3 cm in greatest dimension and therefore in identifying patients who need closer surveillance or earlier aggressive treatment