title: T1 high-grade bladder carcinoma outcome: the role of p16, topoisomerase-IIα, 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 that is 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 single T1HG bladder carcinoma ≤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 immunohistochemical detection of galectin-3, CD44, E-cadherin (E-CAD), CD138, p16, survivin, HYAL-1, and topoisomerase-IIα in 92 randomly selected specimens at participating institutions. Topoisomerase-IIα expression was identified as a predictor of disease-free survival. p16, survivin, and E-CAD 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 single T1HG bladder carcinoma ≤3 cm in greatest dimension and therefore in identifying patients who need closer surveillance or earlier aggressive treatment.
authors.affiliation: Histopathology and Molecular Diagnostics, University Hospital Careggi, Florence, Italy. Electronic address: mariarosaria.raspollini@unifi.it.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Raspollini
authors.affiliation: UGC Anatomía Patológica, Complejo Hospitalario de Jaén, Jaén, Spain.
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Luque
authors.affiliation: Departamento de Anatomia Patologica, Hospital de Cabueñes, Gijon, Asturias, Spain.
authors.forename: Carmen Luz
authors.initials: CL
authors.lastname: Menendez
authors.affiliation: Division of Pathology University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bollito
authors.affiliation: Anatomic Pathology, Department of Pathology, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Anatomic Pathology, Department of Pathology, University of Verona, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Urology Department, Maimonides, Institute of Biomedical Research (IMIBIC), Reina Sofia Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Blanca
authors.affiliation: Histopathology and Molecular Diagnostics, University Hospital Careggi, Florence, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.affiliation: Department of Urology, University Hospital Careggi, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Minervini
authors.affiliation: Unit of Anatomical Pathology, Department of Surgery, Faculty of Medicine, Cordoba, Spain; Champalimaud Clinical Center, Lisbon, Portugal.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
mesh_terms: D000368:Aged; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis*; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D000077022:Survivin; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C000614131:CDKN2A protein, human; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D004250:DNA Topoisomerases, Type II
keywords: Bladder cancer; E-cadherin; Progression; Survivin; T1; Topoisomerase-IIα; p16