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Correlation of Modal Chromosome Number of Cultured Non-Small Cell Lung Carcinomas with DNA Index of Solid Tumor Tissue¹

Department of Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 [J. M. S.] Department of Pathology [D. J. E.] and Section of Molecular Cytogenetics [I. M., J. R. T.], Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; and Department of Pathology, Human Tissue Resource, University of Maryland, Baltimore, Maryland 21201 [J. H. R.]

The modal chromosome number of 13 non-small cell lung carcinomas placed into culture was compared to the DNA index of the tumor tissue as measured by flow cytometry in order to determine whether cytogenetic results from such cultures are representative of the original solid tumor. The modal chromosome number observed in culture, which ranged from 45–146, fell within the range of aneuploidy predicted from the DNA content of the original tissue in all 13 cases. In 7 cases, flow cytometry results showed that the aneuploid G₁/G₀ population of the tumor tissue (DNA index of 1.5 or higher) represented 11–76% of the cells present, while diploid cells (presumably normal tissue) made up the remainder of the population. In these 7 cases, modal chromosome numbers of 61–92 were found in tumor cells cultured from the tissue. In 3 cases, only a diploid or near-diploid population was found by flow cytometry, consistent with the near-diploid modal chromosome number of cultured cells observed (45–55). In 3 cases, the aneuploid G₁/G₀ population (DNA index of 1.5, 1.6, and 3.2) of the original tissue represented only a small fraction of the solid tumor (1–5% of cells). Modal chromosome number found in cells cultured from these 3 cases was 64–69, 62–68, and 136–146, which is in close agreement with the aneuploid peak observed in the tissue. Histological analysis of the tumor tissue in two of the latter cases showed large numbers of infiltrating lymphocytes and/or stromal tissue which could have dominated the measurement by flow cytometry. In the third case, tumor cells made up at least 75% of the specimen examined, implying that part of the population in the "diploid" peak contained tumor cells in this specimen. Only the aneuploid population was detected in culture of this tumor. Agreement between flow cytometry and cytogenetics was found in cases in which metaphase spreads were obtained within a few days of culture as well as after several months. These results indicate that highly aneuploid populations are found in many, but not all, non-small cell lung tumors. Although in some cases multiple populations may exist in the tumor which do not all proliferate in vitro, tumor cells which are found in culture of solid lung carcinomas are representative of the original tumor. Flow cytometry findings in the solid tumors confirmed the findings of aneuploidy observed by cytogenetic analysis.

¹ This work was supported by a grant to J.R.T. from the National Cancer Institute (CA-45745), by grants to J.M.S. from the American Cancer Society (IN-58-28) and the Pharmaceutical Manufacturer's Association Foundation (Research Starter Grant), and by United States Environmental Protection Agency Cooperative Agreement CR-816188 to J.M.S. J.R.T. is a Scholar of the Leukemia Society of America. J.M.S. is a recipient of an American Cancer Society Junior Faculty Award.

² To whom requests for reprints should be addressed, at Department of Pharmacology, University of Pittsburgh, E 1347 Biomedical Science Tower, 13th Floor, Pittsburgh, PA 15261.

Received 12/14/90. Accepted 4/ 1/91.