Correlation between DNA Content, Expression of Ki-67 Antigen of Tumor Cells and Immunophenotype of Lymphocytes from Malignant Pleural Effusions

Abstract

Malignant cells isolated from 26 malignant pleural effusions, collected from patients bearing metastatic carcinoma, were examined using flow cytometry. Expression of Ki-67 antigen, DNA ploidy, S phase fraction, DNA index of tumor cells and the percentage of aneuploid cell populations were determined. Lymphoid cells from the same malignant effusions and from 10 nonmalignant ones were examined using a panel of monoclonal antibodies (mAb) versus several CD antigens. While the percentages of T cells (CD3+, CD4+, CD8+) and B cells (CD19+) did not differ significantly in malignant versus nonmalignant effusions, those of CD56+ lymphocytes were found to be significantly depressed in malignant diploid and malignant aneuploid effusions as compared to benign ones. Expression of IL-2 receptors on lymphocytes, demonstrated by anti-CD25 mAb, was significantly higher in malignant diploid and malignant aneuploid effusions as compared with nonmalignant ones. An increase in the percentage of Ki-67-positive malignant cells was significantly correlated with the decrease of NK cells. S phase fraction, DNA index and the percentage of aneuploid populations did not correlate with the picture of lymphoid cells from pleural effusion. On the other hand, the percentage of Ki-67-positive tumor cells in pleural effusions was inversely proportional to the patients’ survival time, although it was not statistically significant. Our data suggest that the poor prognosis of cancer characterized by the presence of an aneuploid cell population of malignant cells and the high percentage of proliferating cells in pleural effusions can be linked to the depression of NK cells.

Flow cytometric quantitation of natural killer cells and T lymphocytes expressing T‐cell receptors alpha/beta and gamma/delta is not helpful in distinguishing benign from malignant body cavity effusions

“…The Houston VA study population consisted of only men (3). Two other noteworthy studies in the literature examined only pleural effusions caused predominantly (6) or solely (8) by lung cancer. The study by Guzman et al (7) involved only ovarian cancer‐related ascites.…”

“…In numerous reports, the degree of tumor infiltration by NK cells correlates directly with prognosis (1, 2). Comparison of percentage of NK cells in malignant versus benign cavity effusions has yielded conflicting results, with some studies showing a significant increase (3–5), others a significant decrease (6), and still others showing no difference (7, 8). One frequently quoted 1996 study from the Houston Veterans Affairs (VA) Hospital reported a highly statistically significant ( P < 0.00001) association between a high percentage of NK cells and metastatic malignancy in pleural and peritoneal effusions and asserted that (flow cytometric) measurement of NK cells in effusions was “a new, sensitive means of detecting carcinoma” (3).…”

Quantitative analysis of integrin expression in effusions using flow cytometric immunophenotyping

“…In effusion cytology, FCM has previously been used mainly to detect DNA-aneuploid cells populations, [15][16][17][18][19][20] sometimes in combination with immunophenotyping of admixed lymphoid cells. 21,22 Because of the high reproducibility of FCM and its inherent ability to study multiple markers simultaneously, we have recently begun to evaluate its potential role in the diagnosis and characterization of effusion specimens. 12,23,24 Ber-EP4 was found on 94% of carcinomas in the present study, in agreement with our earlier reports.…”

Flow cytometric immunophenotyping of serous effusions and peritoneal washings: comparison with immunocytochemistry and morphological findings

“…To date, flow cytometry has mainly been used to detect aneuploid cell populations, [3][4][5][6][7][8] sometimes in combination with immunophenotyping of admixed lymphoid cells. [9][10][11] The number of natural killer (NK) cells has been used to predict the presence of malignant cells in serous eVusions. 12 However, limited data are available regarding flow cytometric immunophenotyping of epithelial cells in eVusions.…”