Cell Proliferation Measurements by Bromodeoxyuridine or Thymidine Incorporation: Clinical Correlates.

Abstract

T he thymidine or bromodeoxyuridine labeling index (LI) is measured by determining the incorporation of precursor by viable cells in DNA synthesis (S-phase) and is expressed as percent. LI relates closely to cell proliferative rate. More precise measurement requires determination of S-phase duration (Ts), currently not practical for clinical application. LI correlates with mitotic index (MI), 1,2 but LI is much easier to measure accurately, particularly when the proliferative rate is low, because the ratio of labeled to mitotic cells may approach 100 to i. 3 Measurements of LI with tritiated thymidine (3H-dThd) or 5-bromo-2'-deoxyuridine (BrdUrd) administered intravenously or used in vitro with fresh tissue slices are similar. 4 Labeled cells in S-phase are visualized by autoradiography (3H-dThd) or immunohistochemistry (BrdUrd) in tissue sections (Fig 1). Histological identification of cells circumvents problems that can be troublesome with flow cytometry. Our purpose is to describe LI distributions of human tumors that we have studied by a single, standardized technique of in vitro labeling of fresh tissue slices with 3H-dThd or BrdUrd. 5,6 Results show that certain cancers have characteristic high or low proliferative rates, while others have a wide spectrum. The latter probably represent several discrete tumor types that have not been adequately classified by histological criteria. For the former, cell kinetic characteristics can be construed from the histological classification. For the latter, kinetic measurements can provide useful data for subclassification. LIs of some normal tissues are listed in Table 1. Certain tissues are in continuous renewal and have high LIs, whereas others have very low LIs. Some of the latter can respond to cell loss with proliferation