Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival
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DOI:
10.1002/path.894
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发表时间:
2001-08-01
影响因子:
7.3
通讯作者:
Hamilton, PW
Hamilton, PW
中科院分区:
医学1区
文献类型:
--
作者:
Elkablawy, MA;Maxwell, P;Hamilton, PW

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应用细胞凋亡指数(AI)、有丝分裂指数(MI)和p53、bcl-2、p21、mdm 2蛋白免疫反应性对30例结肠腺癌和22例直肠腺癌的癌组织及癌旁正常组织进行了定量检测。将个体特征和组合特征与临床病理参数和患者生存数据相关联,以评估其预后价值。Al增加与bcl-2表达增加(p < 0.008)和包括bcl-2在内的免疫特征显著相关,但与MI、p53、p21或mdm 2无关。Al与Dukes分期从A、B到C的增加显著相关(p < 0.02),但与D无关,而MI显示与所有Dukes分期显著相关(p < 0.05)。AI或MI与预后之间无显著相关性。p53、p21、mdm 2和bel-2的阳性率分别为65.4%、53.8%、65.4%和34.6%。mdm 2与p53(p < 0.03)和p21(p < 0.04)的表达显著相关,且p53在直肠肿瘤中的阳性率更高(p < 0.008)。在单因素生存分析中,bcl-2过表达与更有利的患者生存相关(p < 0.03)。p53+/p21+/bcl-2+和p21+/mdm 2 +/bcl-2+(p < 0.005)、p53+/bcl-2+、p21 + /bcl-2+和mdm 2 + /bcl-2 +(p < 0.01)以及p53 + /p21 +(p < 0.02)的阳性联合模式也与良好的临床结局相关。在多因素考克斯生存分析中,bcl-2(p < 0.016)和Dukes'分期(p < 0.0001)是唯一有意义的独立预后指标。结论:bcl-2免疫反应性与细胞凋亡有关,结合Dukes分期可作为预测大肠癌预后的一种手段。版权所有(C)2001约翰威利父子有限公司
The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased Al was significantly associated with increased bcl-2 expression (p < 0.008) and the immunoprofiles that included bcl-2, but not with MI, p53, p21 or mdm2. Al was significantly associated with increased Dukes' stage from A, B to C (p < 0.02) but not D, while MI showed a significant association with all Dukes' stages (p < 0.05). No significant association was found between either Al or MI and prognosis. p53, p21, mdm2, and bel-2 positivity were detected in 65.4%, 53.8%, 65.4%, and 34.6% of cases, respectively. mdm2 was significantly associated with p53 (p < 0.03) and p21 (p < 0.04) expression and p53 immunoreactivity was more prevalent in rectal tumours (p < 0.008). In univariate survival analysis, bcl-2 overexpression was associated with more favourable patient survival (p < 0.03). Positive combined patterns p53+/p21+/bcl-2+ and p21+/mdm2+/bcl-2+ (p < 0.005); p53+/bcl-2+, p21 + /bcl-2+, and mdm2 + /bcl-2 + (p < 0.01); and p53 + /p21 + (p < 0.02) were also associated with favourable clinical outcome. In multivariate Cox survival analysis, bcl-2 (p < 0.016) and Dukes' stage (p < 0.0001) were the only significant independent prognostic indicators. In conclusion, bcl-2 immunoreactivity was associated with apoptosis and could be used in combination with Dukes' stage as a means of predicting prognosis in colorectal cancer. Copyright (C) 2001 John Wiley & Sons, Ltd.