Cellular DNA content as a marker of neoplasia in man

Abstract

Cellular DNA content was determined by means of flow cytometry with the use of DNA specific fluorochromes (ethidium bromide and mithramycin) in 516 human tissue samples from 440 subjects. Compared to human granulocytes as diploid reference standard, there was a 91 percent incidence of DNA content abnormality difference in DNA content of tumor G 1 0 cells indicating aneuploidy in 118 patients with neoplastic disease (including nine patients who lacked histopathologic evidence of malignancy at the time of study). Ninety-four percent of aneuploid tumors were hyperdiploid. Except for six solid tumors with biclonal abnormalities in DNA content, the remainder of neoplasms were characterized by uniform DNA content with little dispersion (small coefficient of variation of tumor G 1 0 populations). For the entire group of patients with malignant disease, three modal values of DNA content were recognized at low-degree hyperdiploidy, near triploidy and tetraploidy. Except for the prevalence of high-degree hyperdiploidy in melanomas and low-degree hyper- and hypodiploid abnormalities in malignant lymphomas, significant disease-specific patterns of abnormal DNA content were not apparent. The magnitude of ploidy abnormality was further influenced by patient age and proliferative activity of the tumor. Female patients displayed a preponderance of small-degree hyperdiploid and tetraploid tumors, whereas near-triploid abnormalities prevailed among male patients, who also harbored five of six biclonal tumors. Tumor cell ploidy did not vary among different sites of disease and upon sequential long-term follow-up examination. All 121 benign tumors had a diploid DNA content. Among the group of 209 patients with normal histology or reactive changes were seven patients with a previously established diagnosis of cancer with ploidy abnormality. This discrepancy indicates that monodispersal of the entire tissue aliquot for DNA flow cytometry is superior to histologic examination of focal neoplasia. There were two patients, one with recurrent benign pleural effusions and one with reactive lymphadenopathy, with ploidy abnormality by DNA content in whom malignant lymphoma developed. We conclude that flow cytometry of cellular DNA content is a rapid, objective, quantitative and sensitive method to determine a highly specific and stable tumor cell marker.