title: Identification of high-risk patients by assessment of nuclear Ki-67 expression in a prospective study of endometrial carcinomas.
abstract: For patients with localized endometrial carcinoma at primary operation, there is a definite need for more specific prognostic parameters to select patients for adjuvant therapy. The purpose of this study was to evaluate the applicability and prognostic significance of markers for tumor cell proliferation (S phase fraction and Ki-67 expression) among endometrial carcinoma patients, relative to the information derived from established clinicopathological variables including DNA and receptor analyses. In a prospective study of 115 patients treated for endometrial carcinoma, fresh tumor tissue was collected for assessments of ploidy, S phase fraction and hormone receptor concentrations. Ki-67 expression was assessed immunohistochemically on sections from formalin-fixed and paraffin-embedded tumor specimens. These variables were examined together with traditional clinicopathological features in univariate and multivariate (Cox proportional hazards regression model) survival analyses. The median follow-up time for the survivors was 9 years (range, 5-15), with no patient lost due to insufficient follow-up information. The expression of Ki-67 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.0004), histological type (P = 0.03), and histological grade (P = 0.0001). S phase fraction was significantly associated with histological grade (P = 0.02), whereas the association with histological type was of borderline significance (P = 0.07). In univariate analyses, survival was significantly influenced by FIGO stage (P <0.0001), histological type (P = 0.0002), histological grade (P = 0.002), ploidy (P = 0.015), S phase fraction (P = 0.017), progesterone receptor concentration (P = 0.02), and Ki-67 expression (P <0.0001). In Cox regression analysis, FIGO stage (hazard ratio, 11.7; 95% confidence interval, 4.3-32.1) and Ki-67 (hazard ratio, 8.7; 95% confidence interval, 3.0-25.2) were the only variables with independent prognostic impact. When patients whose tumors were confined to the uterus were analyzed separately, Ki-67 was the only variable with an independent prognostic importance. Ki-67 expression was superior to S phase fraction both in applicability and prognostic value. FIGO stage and Ki-67 expression were the only variables with independent prognostic impact in Cox regression analysis. Ki-67 expression is assessed on the histological specimens taken routinely, with no separate sampling technique; this should make it easy to use in a routine setting.
authors.affiliation: Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway. hsalvese@genetics.uchicago.edu
authors.forename: H B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: O E
authors.initials: OE
authors.lastname: Iversen
authors.forename: L A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis* / Q000096:biosynthesis; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D016196:S Phase / Q000502:physiology; D016019:Survival Analysis
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins