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Labeling Index in Clinical Specimens Estimated by the Antinucleoside Antibody Technique¹

Departments of Radiology [T. H. C., D. L., F. E., R. B.] and Pathology [M. J.], Albert Einstein College of Medicine, Bronx 10461, and Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032 [K. C. H.]

The labeling index was estimated in human tumor biopsies with a new method in which antinucleoside antibody and immunoperoxidase staining are used. Excellent agreement of the [³H]thymidine autoradiography labeling index and the antinucleoside immunoreactivity labeling index was obtained in cell aspirates from solid tumor and fluid specimens taken before radiation or chemotherapy as well as in serial tumor samples taken during therapy. The new method was also applied to biopsies of solid tumor specimens, for which the [³H]thymidine autoradiography method is not generally applicable. Fifteen pretreatment human mammary adenocarcinomas were examined. The mean labeling index was 10.8%, in good agreement with results of others who used [³H]thymidine autoradiography. Biopsies from eight patients with head and neck cancers were examined by the new method to learn whether their pretreatment labeling indices were predictive of a good response to a combination chemotherapy regimen.

Before application of antinucleoside antibody, frozen sections must be treated with ribonucleases. We found that, with some specimens, antinucleoside antibody immunoperoxidase labeling indices were spuriously higher without the ribonuclease pretreatment; probably this was due to interference from immunoreactive nuclear RNA.

These results confirm previous studies with cell cultures and animal tumor models, indicating that the new method is a reliable way to estimate the proportion of cells in DNA synthesis in biopsies of human tumors. Results may be obtained in 2 hr by a relatively simple method with potentially wide application. Correlation of pretreatment labeling indices with tumor responses to therapy and scheduling of chemotherapy or radiation therapy after clinical synchronization of the tumor cells are some of the potential clinical applications.

¹ Research supported in part by American Cancer Society Grant PDT-29B, The Burroughs Wellcome Fund, Mildred Werner League for Cancer Research of Great Neck, N. Y., and NIH Grants 5T-32-CA-09173 and CA-20679.

² Recipient of a Jane and Arnold Ginsburg Fellowship in Radiology. To whom requests for reprints should be addressed. at Department of Radiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, N. Y. 10461.

Received 9/ 9/77. Accepted 1/11/78.