BROMODEOXYURIDINE LABELING FOR S-PHASE MEASUREMENT IN BREAST-CARCINOMA

Background. The S-phase fraction relates to proliferation, an importan t determinant of tumor behavior, and has been measured most accurately with the DNA precursor tritiated thymidine (TT). The TT labeling inde x (LI) is a strong stage-independent prognostic indicator for breast c arcinoma. The thymidine analogue 5-bromodeoxyuridine (BrdU) is also in corporated into DNA and has the advantage over TT of immunohistochemic al detectability rather than requiring autoradiography, but it is less well studied in breast carcinoma. This report demonstrates the equiva lence of TT and BrdU LI and explores the relationships between LI and other biologic measurements. Methods. The LI of 234 consecutive breast carcinomas were measured with TT as was a subsequent series of 450 ca ses with BrdU, both by incubation in vitro. Results. The mean BrdU LI was 6.4 +/- 0.3% in comparison with 6.9 +/- 0.4% in the prior TT serie s. LI was unaffected by storage for 24 hours at 4-degrees-C before lab eling with BrdU. The BrdU and TT LI both correlated (1) positively wit h tumor size, histologic type, nuclear size, the number of axillary me tastases, the level of DNA ploidy, and the percent S-phase by flow cyt ometry and (2) negatively with the age of the patient and the levels o f estrogen receptor and progesterone receptor measured either by ligan d binding or by immunohistochemistry. Conclusions. BrdU labeling in vi tro was an advantageous method for measuring S-phase fraction in breas t carcinoma that produced results comparable to those from TT labeling . It should be equally effective for breast cancer kinetic classificat ion and prognosis and is a suitable standard to evaluate newer methods for measuring cellular proliferation.