title: Cell cycle kinetics in malignant lymphoma studied with in vivo iododeoxyuridine administration, nuclear Ki-67 staining, and flow cytometry.
abstract: Cell cycle kinetics of malignant lymphoma were investigated using in vivo labeling with iododeoxyuridine (IdUrd) and subsequent flow cytometry (FCM) of IdUrd/DNA and Ki-67/DNA. This approach provides an extensive cell kinetic profile from only one single tumor biopsy, including data upon the percentage of S-phase cells, the IdUrd labeling index (LI), Ki-67-derived growth fraction, duration of the S-phase, duration of the G1-phase, potential doubling time, cell production rate, and total cell cycle time. Tissue samples from 33 patients were studied: non-Hodgkin's lymphoma (NHL; n = 22), Hodgkin's disease (HD; n = 7), and reactive hyperplasia (n = 4). In NHL, the percentage of S-phase cells, LI, growth fraction, duration of the S-phase, and cell production rate were significantly correlated with the histologic malignancy grade according to the Working Formulation (P < or = .02). Data found in HD were not essentially different from those in low-grade NHL and reactive hyperplasia. Remarkably, the duration of the S-phase, the duration of the G1-phase, and the total cell cycle time appeared to be rather independent of histologic malignancy grade within the NHL category. A significant correlation was observed between the IdUrd LI and the percentage of S-phase cells, the growth fraction, the potential doubling time, and the cell production rate (P < .001), but not with the duration of the separate cell cycle phases (P > .05). Our data show (1) that it is feasible to obtain detailed information on the in vivo growth characteristics of malignant lymphoma; and (2) that the transition time through the different cell cycle phases widely varies, even within distinct histologic subgroups.
authors.affiliation: Department of Hematology, University Hospital Nijmegen, The Netherlands.
authors.forename: P P
authors.initials: PP
authors.lastname: Brons
authors.forename: J M
authors.initials: JM
authors.lastname: Raemaekers
authors.forename: M J
authors.initials: MJ
authors.lastname: Bogman
authors.forename: P E
authors.initials: PE
authors.lastname: van Erp
authors.forename: J B
authors.initials: JB
authors.lastname: Boezeman
authors.forename: A H
authors.initials: AH
authors.lastname: Pennings
authors.forename: H M
authors.initials: HM
authors.lastname: Wessels
authors.forename: C
authors.initials: C
authors.lastname: Haanen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002453:Cell Cycle; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D007065:Idoxuridine; D019394:Ki-67 Antigen; D007700:Kinetics; D008198:Lymph Nodes / Q000473:pathology*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D016196:S Phase; D013997:Time Factors
chemical_list: D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D007065:Idoxuridine