Determination of ploidy and proliferative characteristics of human solid tumors by pulse cytophotometry.

Abstract

Abstract Cellular DNA content is a discriminator of cell cycle stage and ploidy. Using pepsin digestion for cell dispersal, a combination of ethidium bromide and mithramycin for DNA fluorochromation, and a new sheath flow chamber in a PHYWE ICP-11 pulse cytophotometer, we obtained DNA histograms with high resolution (coefficient of variation, 2.0 to 7.0; mean, 3.3%) on biopsy samples of solid tumors. There were 78 observations in 26 patients (malignant melanoma, 7; breast carcinoma, 4; lung carcinoma, 3; lymphoma, 3; miscellanceous tumors, 9). Ploidy identification was conducted by mixing tumor cells with human granulocytes. The ratio of peak channel numbers for the G1/Q compartment of tumor cells to that of normal cells was termed the DNA index. All but one patient with multiple myeloma presented unimodal tumor cell DNA distributions. Except for one breast and one colonic carcinoma, all tumors had aneuploid DNA contents. Three patients presented with hypodiploid abnormalities, and the remainder showed varying degrees of hyperdiploidy (DNA index ranged from 1.07 to 2.40 with a mean of 1.60). Among the patients in whom serial DNA distribution analyses were conducted, only one showed an increase in DNA index from 1.08 to 1.52. This patient presented with immunoblastic lymphadenopathy and later progressed into immunoblastic sarcoma. Pretreatment cycle stagerelated DNA distribution patterns varied considerably for the entire patient population and for each diagnostic subgroup. No correlation between ploidy and proliferative cell characteristics was apparent.