Absence of p53 overexpression and favorable response to cisplatin-based neoadjuvant chemotherapy in urothelial carcinomas

Japanese Journal of Cancer Research : Gann
Y KakehiO Yoshida

Abstract

It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 (P=0.0225) and the combination of p53 and mdm2 (P=0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively. Disease-specific survival of the p53-negative group was significantly superio...Continue Reading

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Citations

Oct 26, 2006·World Journal of Urology·Christopher Y Thomas, Dan Theodorescu
Sep 6, 2000·Urologic Oncology·B J Schmitz-DrägerM Heydthausen
Jul 10, 2010·Oral Oncology·Heui June AhnSung Hyun Yang
Jul 9, 2010·Urologic Oncology·Peter J GoebellUNKNOWN International Study-Initiative on Bladder Cancer (ISBC)
Mar 4, 2000·The Urologic Clinics of North America·A F Olumi
Jul 19, 2014·Critical Reviews in Clinical Laboratory Sciences·Francesca SanguedolceLuigi Cormio
May 17, 2003·Der Urologe. Ausg. A·M-O GrimmW A Schulz
Jul 27, 2017·Pharmacogenomics·Tahlita Cm Zuiverloon, Dan Theodorescu
Jun 11, 2005·The Journal of Urology·Jun WatanabeOsamu Ogawa
Jul 16, 2013·Current Opinion in Urology·Joaquim BellmuntAnna Orsola

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