title: Negative p53/positive p21 immunostaining is a predictor of favorable response to chemotherapy in patients with locally advanced bladder cancer.
abstract: The relationship between clinical response to DNA-damaging drugs and p53 and p21 status in patients with locally advanced transitional cell carcinoma (TCC) of the bladder was assessed. The response to intraarterial chemotherapy (IAC) comprising 100 mg / m(2) of cisplatin (CDDP) and 40 mg / m(2) of pirarubicin (THP) and the prognosis were assessed in 23 patients (the mean follow-up period was 19 months). The p53 gene status of tumors was analyzed at exons 5 - 8 using polymerase chain reaction-single strand conformation polymorphism analysis in 19 patients, and paraffin-embedded tumor sections were immunostained for p53 and p21 in 23 patients. The overall objective response rate (incidence of good responders) was 70%. The negative p53 group (n = 17) showed a significantly higher objective response rate than the positive p53 group (n = 6) (82% vs. 33%; P = 0.045). The p53 gene status or p21 staining status was not significantly associated with responsiveness. When the p53 and p21 immunostaining results were combined, good responders were more accurately predicted than by p53 staining status alone; the negative p53 / positive p21 group (n = 12) showed an objective response rate of 92%, which was significantly higher than that of the positive p53 and / or negative p21 group (45%, n = 11) (P = 0.027). Cause-specific survival of the negative p53 group was significantly superior to that of the positive p53 group (P = 0.015). Negative p53 / positive p21 immunostaining is a possible predictor of favorable chemotherapeutic response in patients with TCC of the bladder.
authors.affiliation: Department of Urology, Dokkyo University School of Medicine, Shimotsuga-gun, Tochigi 321-0207, Japan. f-koga@wine.plala.or.jp
authors.forename: F
authors.initials: F
authors.lastname: Koga
authors.forename: S
authors.initials: S
authors.lastname: Kitahara
authors.forename: K
authors.initials: K
authors.lastname: Arai
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Sumi
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53