Abdel-Moneim I, Melamed M R, Darzynkiewicz Z, Gorczyca W
Department of Pathology, New York Medical College/Westchester Medical Center, Valhalla, New York, USA.
Anal Quant Cytol Histol. 2000 Oct;22(5):393-7.
To examine the relationship between apoptosis and proliferation in a series of human solid malignant tumors, making use of objective, reproducible techniques newly developed for laser scanning cytometry (LSC).
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 with DNA measurement on aliquots of cell suspensions obtained by mechanical dissociation of fresh tumors and placed on microscope slides.
The number of cells undergoing apoptosis varied from 0.5% to 28.1% (average, 5.4 +/- 6.0). Aneuploid tumors showed a higher percentage of apoptotic cells (7.9 +/- 7.2) as compared to diploid tumors (3.4 +/- 4.0). Tumors with the greatest number of apoptotic cells on LSC also had the largest 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 +/- 13.3%).
Overall, there was a very weak or no correlation between apoptosis and proliferation. However, a subset of aneuploid tumors had a high percentage of cells positive for Ki-67 and low percentage of apoptotic cells. Diploid tumors did not show any correlation between apoptosis and proliferation, 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-up studies that include more cases and clinical data. Here we have shown that LSC is a powerful new tool of potential clinical value for fast, objective analysis of apoptosis, proliferation and DNA ploidy in solid malignant tumors.
利用激光扫描细胞术(LSC)新开发的客观、可重复技术,研究一系列人类实体恶性肿瘤中细胞凋亡与增殖之间的关系。
通过用异硫氰酸荧光素(FITC)偶联核苷酸对DNA链断裂进行原位末端标记来检测细胞凋亡。用Ki-67抗体检测细胞增殖。对通过新鲜肿瘤机械解离获得的细胞悬液等分试样进行DNA测量时,独立且同时检测这两个参数,并将其置于显微镜载玻片上。
发生凋亡的细胞数量在0.5%至28.1%之间(平均为5.4±6.0)。与二倍体肿瘤(3.4±4.0)相比,非整倍体肿瘤显示出更高比例的凋亡细胞(7.9±7.2)。在LSC上凋亡细胞数量最多的肿瘤在光学显微镜检查中凋亡细胞数量也最多。被Ki-67标记的细胞数量在1.7%至56.7%之间(平均为20.0±15.5)。非整倍体肿瘤的特征是Ki-67指数较高(平均为28.3±14.3%),高于二倍体肿瘤(13.2±13.3%)。
总体而言,细胞凋亡与增殖之间存在非常弱的相关性或无相关性。然而,一部分非整倍体肿瘤的Ki-67阳性细胞比例高,凋亡细胞比例低。二倍体肿瘤的细胞凋亡与增殖之间未显示出任何相关性,尽管其中许多肿瘤的凋亡指数和增殖指数均较低。这些差异是否具有预后意义仍有待在纳入更多病例和临床数据的后续研究中确定。在此我们已表明,LSC是一种具有潜在临床价值的强大新工具,可用于快速、客观地分析实体恶性肿瘤中的细胞凋亡、增殖和DNA倍性。