Non‐small‐cell lung carcinoma: Tumor characterization on the basis of flow cytometrically determined cellular heterogeneity

Abstract

Some 150 tumor specimens from 49 patients with non-small-cell carcinoma of the lung (23 epidermoid, 14 adenocarcinoma, 12 large-cell carcinoma) and three with nonneoplastic lung disease were analysed for cellular DNA content by flow cytometry. Monodispersed cells were stained with ethidium bromide and mithramycin. Normal specimens and samples from patients with nonneoplastic disease constantly yielded a single cell population with diploid DNA content. Twenty of 23 epidermoid carcinomas exhibited one or more than one aneuploid subpopulation. Ten of 12 largecell carcinomas were characterized by one aneuploid clone and 2/12 by two aneuploid clones. Adenocarcinoma exhibited multiclonal cell subpopulations (one to five aneuploid clones). Further information has been obtained on the differential presence of clones in various tumor areas and in infiltrated lymph nodes. These tumors appear characterized by a remarkable degree of cellular heterogeneity. The cytometric ploidy level(s) and the cell population multiclonal structure yield, in comparison with, and in addition to, pathology, indications of possible clinical interest. A correlation between the clonal DNA content and a prognostic parameter such as the tumor mass doubling time has been demonstrated.

DNA and S‐phase distribution and incidence of metastasis in human primary lung carcinoma

“…Flow cytometry provides a fast and precise method for determination of DNA ploidy and distribution of the cell cycle in tumors. Earlier studies of lung using flow cytometry have shown an aneuploid DNA content in 85% of the primary lung tumors (4,19,22,26,28). The clinical implication of DNA aneuploidy has been examined in various tumor types and in general has been associated with a poor prognosis (2,3,9,11,13,25,28,34).…”

TORAKOCHIRURGIA DNA ploidy as an independent prognostic factor: 10-year results in a group of patients surgically treated for squamous cell lung cancer

“…One such factor is genetic instability, observed by geneticists and molecular biologists, which co-occurs with malignant tumors and is manifested through the abnormal DNA content of cancer cells. The first reports on the prognostic significance of aneuploidy (abnormal amount of DNA) in lung cancer date from the late 1980s [1][2][3][4]. The relatively few reports that have appeared since then are quite inconsistent as to the prognostic significance of ploidy [5][6][7][8][9] This research is a continuation of studies, the early results of which were published in 2000 and 2005 [10,11] The current focus is on the analysis of the effect of aneuploidy on 10-year survival rates in the group of patients treated surgically for squamous cell lung cancer.…”

Flow cytometric determination of DNA ploidy level in nuclei isolated from paraffin‐embedded tissue

“…With the introduction of flow cytometry it has become possible to study karyotypic abnormalities as reflected in DNA content (aneuploidy) in both haematological and solid tumors without being limited to the availability of metaphase cells. So far a correlation between aneuploidy and wellknown prognostic markers has been described for various solid tumors (1,(7)(8)(9)(10). Since DNA flow cytometry required until recently fresh unfixed material, the progress in studies relating aneuploidy to disease-free interval and overall survival has been slow.…”