Cytologic Manifestations of Neoplastic Transformation In Vitro

Abstract

Our objective was to test whether cytologic diagnoses of neoplastic transformation could be made accurately on cultured cells in vitro. Cytologic criteria of malignancy as applied to tissues or exfoliated cells in vivo served as guidelines for the diagnoses in vitro. Diagnosis was made on stained coverslip preparations sent coded from Bethesda to Providence. Neoplastic state was determined at Bethesda by implantation of samples of the tissue culture cells in compatible hosts for assay of their capacity to grow progressively as invasive, serially transplantable neoplasms. Several populations of mixed cell types from embryos of the mouse, hamster, and rat were followed during long-term culture. Of the 12 cell lines initiated, all but one underwent neoplastic transformation. Most lines undergoing such transformation showed a progression of cytologic changes in the following order: increase in cytoplasmic basophilia, increase in number and size of nucleoli, increase in nuclear:cytoplasmic ratio, retraction of cytoplasm, and formation of clusters and cords of cells. Although a few cultures that tested as non-neoplastic or borderline showed certain of the early changes in some cells, all cultures showing the first 4 or 5 changes gave rise to sarcomas in vivo. Diagnoses of 93% of the 95 cultures were consistent with results of in vivo assays. This group of cytologic changes looks promising for further tests, analyses, and possible quantitation.