S‐phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine

Abstract

One hundred fifty-four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S-phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR-labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1%, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Nonmalignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well-defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.

Enhanced Polymer One-step Staining for Proliferating Cell Nuclear Antigen (EPOS-PCNA) in NR-S1 Tumors of Mouse Tongues. Comparison with the PCNA and Bromodeoxyuridine (BrdU) Immunohistochemistry.

“…However, the use of BrdU immunohistochemistry requires in vivo or in vitro administration of BrdU [10,15]. The Ki-67 method was formerly used only on fresh frozen sections; retrospective studies with archival materials were therefore not possible, but a new monoclonal antibody, MIB-1 has been recently developed to react with the same antigenic epitope [12].…”

“…BrdU immunostaining technique has been widely used for studying cell kinetics in tumors, and was proven to be useful as biological markers [6,10]. However, BrdU immunohistochemistry is time-consuming and not easily applicable for routine clinical samples.…”

Cell kinetic analysis of murine squamous cell carcinomas: a comparison of single versus double labelling using flow cytometry and immunohistochemistry

“…Alternatively, non-radioactive techniques have been developed using two different thymidine analogues which can be recognised by specific antibodies. However, cross-reactivity of these antibodies could be a problem in both IHC methods (Shibui et al, 1989;Hoshino et al, 1986) and FCM (Bakker et al, 1989;Raza, 1987 (Figure 3a). T. estimates have also been derived from quantitative analysis of nuclear uptake of one single radioactive DNA precursor (Dormer, 1973).…”

An indirect immunofluorescence double staining procedure for the simultaneous flow cytometric measurement of iodo‐ and chlorodeoxyuridine incorporated into DNA

“…A mouse monoclonal anti-BrdUrd antibody from Becton Dickinson used in a 1:2 dilution binds to all halogenated deoxyuridines but, when the cells were extensively washed with Tris buffer with a high salt concentration, almost no binding to CldUrd was observed. An immunofluorescence procedure was developed, based on these primary antibodies, raised in different species (rat and mouse), in combination with highly purified second antibodies: FITC conjugated goat antirat and TexasRed conjugated goat antimouse.Key terms: Immunochemistry, double staining procedure, IdUrd, CldUrd, flow cytometry, cell kineticsThe study of experimental and human tumors has been facilitated by the recent introduction of immunocytochemical procedures for the detection of halogenated deoxyuridines incorporated into cellular DNA (1,2,(4)(5)(6)(7)(8)(9)(10)(11)13,15,17,18). These methods are rapid and easy to perform, and data from a single sample can provide several cell kinetic parameters (cf.…”

“…The study of experimental and human tumors has been facilitated by the recent introduction of immunocytochemical procedures for the detection of halogenated deoxyuridines incorporated into cellular DNA (1,2,(4)(5)(6)(7)(8)(9)(10)(11)13,15,17,18). These methods are rapid and easy to perform, and data from a single sample can provide several cell kinetic parameters (cf.…”