title: Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67.
abstract: To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki-67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.
authors.affiliation: Department of Pathology, University of Arizona Health Sciences Center, Tucson.
authors.forename: T M
authors.initials: TM
authors.lastname: Grogan
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
authors.forename: C M
authors.initials: CM
authors.lastname: Spier
authors.forename: D J
authors.initials: DJ
authors.lastname: Slymen
authors.forename: J A
authors.initials: JA
authors.lastname: Rybski
authors.forename: C S
authors.initials: CS
authors.lastname: Rangel
authors.forename: L C
authors.initials: LC
authors.lastname: Richter
authors.forename: T P
authors.initials: TP
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D002648:Child; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008224:Lymphoma, Follicular / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D009687:Nuclear Proteins