No abstract

No abstract

In vitro measurement of the thymidine labeling index (TLI) of solid tissues requires hyperbaric oxygenation and is potentiated by blockade of thymidylate synthetase by 5-fluoro-2'-deoxyuridine (FUdR) to favor uptake of tritiated thymidine (3H-TdR). Hyperbaric oxygenation can be achieved in a simple system through injection of oxygen into rubber-stoppered test tubes. Incubations are carried out in Hanks' balanced salt solution in a shaker bath at 37 C for 2 hours; an FUdR concentration of approximately 1 micron is optimal. Autoradiographic exposure for 1 week or less is sufficient for TLI measurements on human tissues. With 3 to 4 atmospheres oxygen tension, incorporation of 3H-TdR is sufficient for TLI measurement throughout slices of tissue cut 1 mm thick or less. Mincing of tissue is not necessary, and the anatomic continuity seen in ordinary histological preparations is preserved. A gradient of labeling intensity is present from the surface to the interior of the tissue, but sufficient intensity of labeling for detection of DNA synthesis can be achieved in the interior of the section. The gradient can be reduced only slightly by prior incubation in 3H-TdR with hyperbaric oxygen at 0 C. The method permits TLI measurements on the same specimens, including needle biopsies, that are used for pathologic diagnosis.

The thymidine labeling indice (TLI) of normal and abnormal epithelium in the human breast was measured in 108 surgical specimens. The mean values for various histologic entities were: normal lobule 0.91%; normal postlobular duct 0.71%; lobular hyperplasia 0.82%; ductal hyperplasia, lobular cell type 0.74%; intraductal hyperplasia 0.79%; papillary intraductal hyperplasia 1.02%; blunt duct adenosis 0.68%; cyst 0.56%; infiltrating carcinoma 6.82%; carcinoma in situ 5.53%. The TLI of the normal lobule declined significantly with increasing age, but that of the normal postlobular duct did not. Before the menopause, the mean TLI of the normal lobule was 1.01%, and that of the normal postlobular duct was 0.75%. After the menopause the values had declined to 0.26% and 0.41%, respectively. These findings indicated that the lobules are more sensitive to stimulation by sex steroids than the postlobular ducts. The TLIs of the various benign proliferative entities were not significantly correlated with age, and like the normal lobule and postlobular duct were near the low end of the range of TLI of breast carcinoma. Benign proliferative entities with TLIs in the high part of the breast carcinoma range were not encountered.

No abstract