Proliferation and apoptosis in solid tumors - Analysis by laser scanning cytometry

OBJECTIVE: To examine the relationship between apoptosis and proliferation in a series of human solid malignant tumors, making use of objective, repro ducible techniques newly developed for laser scanning cytometry (LSC). STUDY DESIGN: Apoptosis was detected by in situ end labeling of DNA strand breaks with FITC-conjugated nucleotide. Proliferation was detected by Ki-67 antibody. Two parameters were detected independently and simultaneously wi th DNA measurement on aliquots of cell suspensions obtained by mechanical d issociation of fresh tumors and placed on microscope slides. RESULTS: The number of cells undergoing apoptosis varied from 0.5% to 28.1% (average, 5.4 +/- 6.0). Aneuploid turners showed a higher percentage of ap optotic cells (7.9 +/- 7.2) as compared to diploid tumors (3.4 +/- 4.0). Tu mors with the greatest number of apoptotic cells on LSC also had the larges t number of apoptotic cells on light microscopic examination. The number of cells labeled by Ki-67 ranged from 1.7% to 56.7% (average, 20.0 +/- 15.5). Aneuploid tumors were characterized by a higher Ki-67 index (average, 28.3 +/- 14.3%) than the diploid tumors (13.2 +/- 23.3%). CONCLUSION: Overall, there was a very weak or no correlation between apopto sis and proliferation However, a subset of aneuploid tumors had a high perc entage of cells positive for Ki-67 and low percentage of apoptotic cells. D iploid tumors did not show any correlation between apoptosis and proliferat ion, although many of those tumors had both low apoptotic and proliferative indices. Whether those differences are of prognostic significance remains to be determined in follow-np studies that include more cases and clinical data. Here we have shown that LSC is a powerful new tool of potential clini cal value for fast, objective analysis of apoptosis, proliferation and DNA ploidy in solid malignant tumors.