A NEW METHOD FOR ANALYZING THE CELL-KINETICS OF HUMAN BRAIN-TUMORS BY DOUBLE-LABELING WITH BROMODEOXYURIDINE INSITU AND WITH LODODEOXYURIDINE INVITRO

Background. Cell kinetics studies performed with immunohistochemical techniques to estimate the S-phase fraction have elucidated the proliferative potential of individual brain tumors. Methods. The authors developed a new double-labeling method that enables other cell kinetics variables, including the duration of the S-phase (Ts) and the potential doubling time (Tp), to be measured from a single biopsy specimen. Using this method, 100 brain tumors were labeled with bromodeoxyuridine (BUdR) in situ and with iododeoxyuridine in vitro; labeled cells were identified by double staining with immunogold-silver and alkaline phosphatase techniques. Results. Ts was fairly uniform (mean, 9.2 +/- 2.1 hour [+/- standard deviation]); range, 6.0-13.7 hours), but Tp varied from 1 day to more than 2 months. The Tp values correlated closely with the BUdR labeling index (LI), or S-phase fraction, and can be calculated from the equation: Tp = 26.9/LI1.02 (r = 0.98, P < 0.005). Conclusions. This new method facilitates the quantitation of the proliferative potential of individual brain tumors. The S-phase fraction, Ts, and Tp can be calculated from analysis of a single biopsy specimen. This method can be used to estimate the prognosis of individual patients with brain tumors and to select treatment modalities more directly than is possible with single-labeling studies with BUdR.