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

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.

Human pathology. 2016 Jul 26 [Epub ahead of print]

Maria Rosaria Raspollini, Rafael J Luque, Carmen Luz Menendez, Enrico Bollito, Matteo Brunelli, Guido Martignoni, Rodolfo Montironi, Liang Cheng, Ana Blanca, Gianna Baroni, Andrea Minervini, Antonio Lopez-Beltran

Histopathology and Molecular Diagnostics, University Hospital Careggi, Florence, Italy. Electronic address: ., UGC Anatomía Patológica, Complejo hospitalario de Jaén, Jaén, Spain., Departamento de Anatomia Patologica, Hospital de Cabueñes, Gijon, Asturias, Spain., Division of Pathology University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy., Anatomic Pathology, Department of Pathology, University of Verona, Verona, Italy., Anatomic Pathology, Department of Pathology, University of Verona, Verona, Italy., Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy., Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Urology Department, Maimonides, Institute of Biomedical Research (IMIBIC), Reina Sofia Hospital, University of Cordoba, Cordoba, Spain., Histopathology and Molecular Diagnostics, University Hospital Careggi, Florence, Italy., Department of Urology, University Hospital Careggi, Florence, Italy., Unit of Anatomical Pathology, Department of Surgery, Faculty of Medicine, Cordoba, Spain; Champalimaud Clinical Center, Lisbon, Portugal.