Diagnostic and Biological Implications of Flow Cytometric DNA Content Analysis in Lung Cancer

Flow cytometric DNA content analysis, performed on clinical specimens from patients with lung cancer, was compared with clinical features, histological and/or cytological examination of the same specimen and, in some instances, to chromosome analysis and repeat DNA content analysis of short-term cultures. Tumors from 85% of non-small cell and 83% of small cell lung cancer patients had aneuploid DNA content; multiple aneuploid stem lines were present in 11% of patients. Comparisons with microscopic examination showed that aneuploid cells were detected in 122 of 167 clinical samples containing tumor cells and in 3 of 177 samples microscopically free of tumor. The high false-negative rate, shown to be due in large part to the presence of near-diploid tumor cells, makes single-parameter DNA analysis impractical for use in automated cytology. Short-term cultures of tumor cells, used to confirm that tumors had DNA content indistinguishable from diploid, demonstrated a single near-diploid peak on repeat DNA analysis with or without the addition of diploid lymphocytes and internal DNA standards. Chromosome banding studies showed clonal structural abnormalities with minimal numeric alterations. Survival of small cell lung cancer patients was similar for patients with near-diploid and aneuploid tumors. Cell cycle analysis could be performed in only a minority of samples, and there were no apparent differences in the proliferative fraction between lung cancer cell types. We conclude that flow cytometric DNA content analysis provides useful biological information and is a useful marker for following tumor cell cultures, but multiparameter analyses will be required for use in automated cytology and in cell kinetic studies.