Correlation of malignancy with the intracellular Na+:K+ ratio in human thyroid tumors

Energy-dispersive X-ray microanalysis was applied on human intraoperative biopsy materials of different thyroid tumors. To ensure suitability of these tissue pieces for quantitative microanalysis in freeze-fractured, freeze-dried bulk specimens, sampling was carried out with strictly defined criteria. Benign adenomas and differentiated and anaplastic carcinomas were selected for the studies on the basis of pathohistological investigations of the same specimen. The results of the tumor cells were compared to those obtained in apparently normal human epithelial cells. The number of normal cells analyzed was 349, whereas in the tumors 408, 423, and 891 cells were measured in the benign, differentiated, and anaplastic groups, respectively. Intracellular monovalent contents were calculated as percentage of cell dry mass; then, Na+:K+ molar ratios were calculated for each cell individually. Due mostly to the increase of Na+ content, the distribution histograms of the Na+:K+ molar ratio show an increase in the number of cells with a higher Na+:K+ ratio with increasing malignancy of the tumors studied. The differences proved to be statistically highly significant by the chi 2 test. Thus, in human thyroid, increasing malignancy is associated with increasing intracellular Na+:K+ ratio. The results give further support to the theory of C. D. Cone (J. Theor. Biol., 30: 151-181, 1971) according to which the sustained depolarization of the cell membrane results in an increased rate of cell division.