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Quantitative Tumor Cytochemistry—G. H. A. Clowes Memorial Lecture¹

Institute of Tumor Pathology, Karolinska Hospital, Karolinska Institutet, S 104 01 Stockholm, Sweden

Quantitative optical cytochemistry permits the determination of many different parameters in whole cells or parts of cells. Total amounts of DNA, RNA, and protein and/or the amounts of these substances in nucleus or nucleolus are examples. Techniques in this field have contributed considerably to the development of our present conceptions of normal cell growth and regulation. Normal cell study has, however, predominated so that tumor work has not yet been very extensive, even though quite early on, in the 1940's, a conspicuous cytochemical peculiarity was found in cancers, namely, a pronounced variability between cells with regard to several measurable parameters. The result has been different kinds of technical difficulties, which are especially great in work on tumor material.

However, as years passed, a fair amount of information was accumulated from studies of different parameters in tumors. Only a few years ago this experience clearly indicated that, provided very considerable improvements were made in technique, several cytochemical methods could be used as efficient supplements to morphological cytodiagnostic work, especially in such important clinical fields as preneoplasia identification, malignancy grading, and judgment of the state of growth of, for instance, hormone-stimulated populations and also the distinction, so difficult in morphology, between "atypical hyperplasia" and "truly malignant" states.

In an effort to eliminate the foremost of these technical difficulties, during the last few years we have developed a comprehensive system for large-scale uni- and multiparameter measurements aimed specifically at the types of specimens encountered in cytopathological work. The system is based on cytophotometry in ultraviolet and visible light, interferometry, and fluorometry and also encompasses special arrangements to simplify the identification and recovery of individual cells for different types of study. Instruments for facilitation of the comparison of cytochemical results with morphological findings are also included.

¹ Presented at the 1978 Meeting of the American Association for Cancer Research, in Washington, D. C. A major part of the early work described was supported by the Wallenberg Foundation, Swedish Cancer Society and also grants from the NIH (Institute of General Medical Sciences). The recent development of the instrument complex was made possible by grants from the Swedish Cancer Society, the Wallenberg Foundation, the National Cancer Institute (Contract N01-CB-43945), and the Damon Runyon Fund. During the whole period, support has been received from the funds of the Karolinska Institutet.