title: Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors.
abstract: The biological behavior of urothelial carcinomas remains unpredictable. The objective of this study was to determine the prognostic value of Ki-67 index in superficial papillary bladder tumors and to correlate it with the S-phase fraction (SPF) measured by flow cytometry. Three hundred nineteen patients with newly diagnosed superficial (pTa, pT1) bladder tumors were included between September 1990 and April 1992. Patients with bladder carcinoma in situ alone were excluded. We observed 255 pTa tumors and 64 pT1 tumors, whereas 111 lesions were classified as grade G1 and 208 as grade G2-G3. Ki-67 immunostaining was performed on paraffin-embedded material using a 3-step immunoperoxidase procedure with the murine monoclonal antibody MiB1. The relation between Ki-67 expression and prognostic variables (stage, grade, tumor size, multifocality, age, and sex) was investigated by the chi-square test. Cox regression was used to describe the association between Ki-67 and tumor recurrence in 308 patients with follow-up while adjusting for potentially confounding prognostic variables. The frequency of high Ki-67 expression (> or =10%) increased with stage (P = .005) and grade (P = .001), but not with tumor size or multifocality. Two hundred one patients experienced tumor recurrence in a median follow-up of 68 months. Stage, grade, tumor size, and multifocality were all independent predictors of recurrence. Ki-67 index greater than 10% was found to be an independent predictor of tumor recurrence among patients with tumors larger than 3 cm in diameter (HR = 2.05, CI = 1.18-3.55), but not those with smaller size tumors. With regards to the DNA index, a significant but weak correlation was observed between Ki-67 expression and the SPF (Spearman's correlation coefficient = 0.23, P = .004). In addition, aneuploid tumors had significantly higher expression of Ki-67 (22.5%) than diploid tumors (10.1%) (P = .0006). Moreover, patients with DNA aneuploid bladder tumors were more likely to have more than 10% Ki-67-positive cells than those with diploid tumors. In patients with newly diagnosed pTa or pT1 bladder tumors, a Ki-67 index above 10% is an independent predictor of shorter time to recurrence only in those with tumors larger than 3 cm.
authors.affiliation: Centre de Recherche en Cancérologie, Université Laval, Québec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Pfister
authors.forename: L
authors.initials: L
authors.lastname: Lacombe
authors.forename: M C
authors.initials: MC
authors.lastname: Vezina
authors.forename: L
authors.initials: L
authors.lastname: Moore
authors.forename: H
authors.initials: H
authors.lastname: Larue
authors.forename: B
authors.initials: B
authors.lastname: Têtu
authors.forename: F
authors.initials: F
authors.lastname: Meyer
authors.forename: Y
authors.initials: Y
authors.lastname: Fradet
mesh_terms: D000368:Aged; D002455:Cell Division; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016196:S Phase; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: D019394:Ki-67 Antigen