title: Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas.
abstract: pT1 G3 bladder carcinomas are heterogeneous with respect to tumor recurrence and progression. Whereas some urologists treat these carcinomas by repeated transurethral resections often followed by intravesical chemotherapy or BCG instillation, others recommend cystectomy after tumor recurrence or early cystectomy after the initial diagnosis. Our goal was to determine the prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak, and Ki-67 immunoreactivity in these tumors. There were 30 patients with a new histopathological diagnosis of pT1 G3 urothelial carcinoma based on a transurethral resection specimen. Representative sections of these specimens were examined for the above markers. All patients were followed up regularly and were classified as being tumor free or having tumor recurrence or progression. The mean follow-up period was 43 months (range: 8-102 months). Twenty-five patients underwent radical cystectomy and 7 of these (28%) suffered from tumor progression and died of bladder cancer. In 5 patients, surgery was limited to a transurethral resection and 4 of these patients developed superficial tumor recurrence. There was a significant difference in tumor-free survival between patients with p53-immunoreactive (mean: 30 months) and p53-negative tumors (mean: 82 months; p = 0.0341). Bcl-2 positivity was also associated with decreased tumor-free survival (p = 0.043). The other markers had no significant prognostic impact. We conclude that p53 and Bcl-2 immunoreactivity labels the most aggressive pT1 G3 bladder carcinomas.
authors.affiliation: Department of Pathology, University of Mainz, Germany. helmut-karl.wolf@klinikum-lippe.de
authors.forename: H K
authors.initials: HK
authors.lastname: Wolf
authors.forename: C
authors.initials: C
authors.lastname: Stöber
authors.forename: R
authors.initials: R
authors.lastname: Hohenfellner
authors.forename: J
authors.initials: J
authors.lastname: Leissner
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis*; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
chemical_list: C494772:BAK1 protein, human; C494826:BAX protein, human; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein