DNp63 Expression is a Protective Factor of Progression in Clinical High Grade T1 Bladder Cancer pez-Martı´nez, Orit Karni-Schmidt, Dennis M. Bonal, Josep M. Gaya, Juan M. Lo Ferran Algaba, Joan Palou, Humberto Villavicencio, Mitchell C. Benson, Carlos Cordon-Cardo* and Mireia Castillo-Martin* From the Departments of Pathology (OK-S, DMB, MC-M) and Urology (MCB), Columbia University (JMG) and Department of Pathology, Icahn School of Medicine at Mount Sinai (OK-S, DMB, MC-M), New York (CC-C), New York, and Departments of Urology Puigvert, Universitat Auto noma de Barcelona, Barcelona, Spain (JMG, JML-M, JP, HV) and Pathology (FA), Fundacio
Abbreviations and Acronyms BCG ¼ bacillus Calmette-Guerin CIS ¼ carcinoma in situ DSS ¼ disease specific survival HGT1 ¼ high grade T1 MID ¼ muscle invasive disease NMIBC ¼ nonmuscle invasive bladder cancer OS ¼ overall survival RC ¼ radical cystectomy RFS ¼ recurrence-free survival TMA ¼ tissue microarray TUR ¼ transurethral resection Accepted for publication October 20, 2014. Study received institutional review board approval. * Correspondence: Department of Pathology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Pl., New York, New York 10029 (telephone: 212-241-7617; FAX: 646-537-8631; e-mail: [email protected]) and Department of Pathology, Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital (telephone: 212-241-8014; FAX: 212426-5129; e-mail: carlos.cordon-cardo@mssm. edu).
Purpose: Several risk factors have been claimed to predict the progression of clinically high grade T1 bladder tumors. However, these factors are not specific enough to define which patients should be treated immediately with radical cystectomy. Therefore, it is critical to identify molecular markers that can help provide individualized, risk stratified decision making. Our main goal was to evaluate the role of total p63, p53 and DNp63 expression in cases of clinically high grade T1 bladder cancer progression. Materials and Methods: Total p63, p53 and DNp63 expression was analyzed by immunohistochemistry in 134 clinically high grade T1 tumors. We assessed clinical progression to muscle invasive disease or radical cystectomy as a patient outcome end point. Survival analysis was done for recurrence-free, progressionfree, disease specific and overall survival. Results: A total of 132 patients (98.5%) underwent repeat transurethral resection. Cases of early progression (less than 3 months) were excluded from study to avoid under staging. Of the tumors 90 (67.2%) showed DNp63 expression loss. During a median followup of 62.1 months 19 patients (14.2%) progressed to muscle invasive disease. The progression rate was 21.1% in patients with tumors characterized by DNp63 loss but no progression was observed in those with tumors with DNp63 expression (p
Abbreviations and Acronyms BCG ¼ bacillus Calmette-Guerin CIS ¼ carcinoma in situ DSS ¼ disease specific survival HGT1 ¼ high grade T1 MID ¼ muscle invasive disease NMIBC ¼ nonmuscle invasive bladder cancer OS ¼ overall survival RC ¼ radical cystectomy RFS ¼ recurrence-free survival TMA ¼ tissue microarray TUR ¼ transurethral resection Accepted for publication October 20, 2014. Study received institutional review board approval. * Correspondence: Department of Pathology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Pl., New York, New York 10029 (telephone: 212-241-7617; FAX: 646-537-8631; e-mail: [email protected]) and Department of Pathology, Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital (telephone: 212-241-8014; FAX: 212426-5129; e-mail: carlos.cordon-cardo@mssm. edu).
Purpose: Several risk factors have been claimed to predict the progression of clinically high grade T1 bladder tumors. However, these factors are not specific enough to define which patients should be treated immediately with radical cystectomy. Therefore, it is critical to identify molecular markers that can help provide individualized, risk stratified decision making. Our main goal was to evaluate the role of total p63, p53 and DNp63 expression in cases of clinically high grade T1 bladder cancer progression. Materials and Methods: Total p63, p53 and DNp63 expression was analyzed by immunohistochemistry in 134 clinically high grade T1 tumors. We assessed clinical progression to muscle invasive disease or radical cystectomy as a patient outcome end point. Survival analysis was done for recurrence-free, progressionfree, disease specific and overall survival. Results: A total of 132 patients (98.5%) underwent repeat transurethral resection. Cases of early progression (less than 3 months) were excluded from study to avoid under staging. Of the tumors 90 (67.2%) showed DNp63 expression loss. During a median followup of 62.1 months 19 patients (14.2%) progressed to muscle invasive disease. The progression rate was 21.1% in patients with tumors characterized by DNp63 loss but no progression was observed in those with tumors with DNp63 expression (p
