Cör Andrej, Pizem Joze, Gale Nina
Institute for Histology and Embryology, Medical Faculty of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia,
Virchows Arch. 2004 May;444(5):439-46. doi: 10.1007/s00428-004-0997-1. Epub 2004 Mar 25.
Active caspase 3 is considered to be the main executioner caspase in apoptotic process. The mechanisms of apoptosis in laryngeal squamous cell carcinoma (LSCC) have been investigated by examining the expression profiles of pro-caspase 3 and active-caspase 3. The correlation between the two forms of caspase 3 and the p53 status was also determined. LSCCs ( n=65) were studied using immunohistochemistry with antibodies to pro-caspase 3, active-caspase 3 and p53. The expression of pro-caspase 3 was absent or weak in 16 (24.6%), moderate in 21 (32.3%) and strong in 28 (43.1%) cases. Survival curves for different levels of pro-caspase 3 differed, but the differences were not statistically significant. An apoptotic index (AI) was determined by quantifying the active-caspase 3-positive cells. The AI ranged from 0.2% to 9.4% and did not differ among the different levels of pro-caspase 3 expression. Even in cases in which the expression of pro-caspase 3 was considered negative, caspase 3-positive apoptotic cells were found. The AIs were significantly higher in supraglottic tumours compared with glottic counterparts ( P=0.008) and were higher in poorly differentiated tumours compared with well-differentiated and moderately differentiated LSCC ( P=0.06). No correlation between AI and p53 expression was found, although pro-caspase 3 expression trended to be higher in the p53-positive group of LSCC. Our results suggest that the expression of pro-caspase 3, a key executioner caspase in apoptosis, is downregulated in a proportion of LSCC, but this is not associated with decreased apoptotic activity, measured by active-caspase 3 labelling.
活化的半胱天冬酶-3被认为是凋亡过程中的主要执行性半胱天冬酶。通过检测前体半胱天冬酶-3和活化的半胱天冬酶-3的表达谱,对喉鳞状细胞癌(LSCC)的凋亡机制进行了研究。还确定了两种形式的半胱天冬酶-3与p53状态之间的相关性。使用针对前体半胱天冬酶-3、活化的半胱天冬酶-3和p53的抗体,通过免疫组织化学对65例LSCC进行了研究。前体半胱天冬酶-3的表达在16例(24.6%)中缺失或较弱,21例(32.3%)中为中度,28例(43.1%)中为强阳性。不同水平前体半胱天冬酶-3的生存曲线不同,但差异无统计学意义。通过对活化的半胱天冬酶-3阳性细胞进行定量来确定凋亡指数(AI)。AI范围为0.2%至9.4%,在不同水平的前体半胱天冬酶-3表达之间无差异。即使在前体半胱天冬酶-3表达被认为阴性的病例中,也发现了半胱天冬酶-3阳性的凋亡细胞。与声门肿瘤相比,声门上肿瘤的AI显著更高(P = 0.008),与高分化和中分化LSCC相比,低分化肿瘤的AI更高(P = 0.06)。尽管在LSCC的p53阳性组中前体半胱天冬酶-3表达有升高趋势,但未发现AI与p53表达之间存在相关性。我们的结果表明,凋亡中的关键执行性半胱天冬酶——前体半胱天冬酶-3的表达在一部分LSCC中下调,但这与通过活化的半胱天冬酶-3标记测量的凋亡活性降低无关。