Influences on measurement of cellular proliferation by histology and flow cytometry in mammary carcinomas labeled in vivo with bromodeoxyuridine.

Field-selection procedures strongly influence histologically determined bromodeoxyuridine (BrdU) labeling indices (HLIs): For a series of 52 breast carcinomas, "high-labeling" fields had mean 2,000-cell HLIs that were, on average, more than double those for random fields, but the ratio was extremely variable. Although there may be a priori reasons for preferring particular field-sampling techniques, nonstandardized kinetic data from different laboratories will be uninterpretable and therefore of limited clinical application. Also, if heterogeneity of tumor cell proliferation is neglected, it is possible that incomplete or even misleading data may be gained. Total flow cytometric BrdU labeling indices (TLIs) were not, on average, higher or lower than HLIs for the same cases, but individual discrepancies could be pronounced. The best correlation of flow cytometric LIs with HLIs was obtained for aneuploid carcinomas with a restricted labeling index derived for aneuploid (presumptively neoplastic) cells only. Although flow cytometric analysis avoids the statistical problems associated with accurately determining a small percentage from relatively few cells, it lacks precise definition of the character of the cells counted, but even histologic methods are not entirely free of this difficulty.