title: Ki-67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification.
abstract: Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki-67 immunoexpression in low-grade (GI-II) USPC in order to predict the potential outcome of these tumors. P53 and Ki-67 immunoexpression were studied in function of recurrence-free and progression-free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki-67 index (>/=18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression-free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki-67 index into the risk model, single pTa/T1-GI Ki-67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1-G1 with a high risk of recurrence and progression. Ki-67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low-grade USPC, the accuracy of the prognostic discrimination is enhanced.
authors.affiliation: Surgical Oncology Department, Portuguese Institute of Oncology, Porto, Portugal. ucib@ipoporto.min-saude.pt
authors.forename: Lúcio
authors.initials: L
authors.lastname: Santos
authors.forename: Teresina
authors.initials: T
authors.lastname: Amaro
authors.forename: Céu
authors.initials: C
authors.lastname: Costa
authors.forename: Sofia
authors.initials: S
authors.lastname: Pereira
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Bento
authors.forename: Paula
authors.initials: P
authors.lastname: Lopes
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Begoña
authors.initials: B
authors.lastname: Criado
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D014408:Biomarkers, Tumor; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53