Yang Lin, Wu Dong-ying, Xin Yan
No.4 Lab, Cancer Institute, First Affiliatied Hospital, China Medical University, Shenyang 110001, China.
Zhonghua Zhong Liu Za Zhi. 2006 May;28(5):357-60.
To study the level of expression of Caspase-3 protein in precancerous lesions of stomach and its relation to gastric carcinogenesis.
Formalin-fixed paraffin embedded tissues from 184 cases of gastric mucosa biopsy and surgically removed specimens, including gastric cancer (GC, N = 20), chronic atrophic gastritis (CAG, N = 6), atrophic gastritis with intestinal metaplasia (IM, N = 31), atrophic gastritis with dysplasia (DYS, N = 114) and normal controls (N = 13) were examined for expression of Caspase-3 protein and Ki-67 index by SABC immunohistochemistry, and for apoptosis by TdT-mediated dUTP biotin nick end labeling (TUNEL) method. Caspase-3, Ki-67 and TUNEL index were compared in different stages of gastric precancerous lesions and their correlation was analyzed.
The positive index of Caspase-3 protein in severe DYS (29.8% +/- 3.9%) showed no significant difference compared with that in GC (26.9% +/- 3.0%, P > 0.05), but was significantly lower than that in low (58.3% +/- 4.2%) and moderate grade DYS (50.4% +/- 4.8%), CAG (68.3% +/- 3.3%) and IM (70.9% +/- 4.3%, P < 0.05). Caspase-3 positive index was significantly correlated with that of apoptosis detected by TUNEL (r = 0.94, P < 0.05). Ki-67 index in Caspase-3 protein positive group (18.3% +/- 2.2%) was significantly lower than that in Caspase-3 negative group (48.9% +/- 3.1%, P < 0.05).
Caspase-3 protein expression was upregulated in CAG with or without IM and low or moderately low in DYS, while down-regulated in severe DYS and gastric carcinoma, and significantly positively correlated with cell apoptosis. It is suggested that down-regulated expression of Caspase-3 protein somehow contributes to gastric carcinogenesis through an imbalance between cell apoptosis and proliferation.
研究Caspase-3蛋白在胃癌前病变中的表达水平及其与胃癌发生的关系。
采用SABC免疫组化法检测184例胃黏膜活检及手术切除标本（包括胃癌（GC，n = 20）、慢性萎缩性胃炎（CAG，n = 6）、萎缩性胃炎伴肠化生（IM，n = 31）、萎缩性胃炎伴异型增生（DYS，n = 114）及正常对照（n = 13））中Caspase-3蛋白的表达及Ki-67指数，采用TdT介导的dUTP生物素缺口末端标记法（TUNEL）检测细胞凋亡情况。比较胃癌前病变不同阶段的Caspase-3、Ki-67及TUNEL指数，并分析其相关性。
重度异型增生中Caspase-3蛋白阳性指数（29.8%±3.9%）与胃癌（26.9%±3.0%）相比差异无统计学意义（P>0.05），但显著低于轻度（58.3%±4.2%）和中度异型增生（50.4%±4.8%）、CAG（68.3%±3.3%）及IM（70.9%±4.3%，P<0.05）。Caspase-3阳性指数与TUNEL法检测的细胞凋亡指数显著相关（r = 0.94，P<0.05）。Caspase-3蛋白阳性组的Ki-67指数（18.3%±2.2%）显著低于Caspase-3阴性组（48.9%±3.1%，P<0.05）。
Caspase-3蛋白在伴有或不伴有肠化生的CAG中表达上调，在异型增生中呈低或中度表达，而在重度异型增生和胃癌中表达下调，且与细胞凋亡显著正相关。提示Caspase-3蛋白表达下调可能通过细胞凋亡与增殖失衡在胃癌发生中起一定作用。
