Hanna-Morris A, Badvie S, Cohen P, McCullough T, Andreyev H J N, Allen-Mersh T G
Chelsea and Westminster Hospital, London, Imperial College of Science, Technology and Medicine, UK.
J Clin Pathol. 2009 Apr;62(4):325-30. doi: 10.1136/jcp.2007.054643. Epub 2008 May 12.
Loss of control of mucosal crypt cell proliferation resulting in a hyperproliferative field change occurs early in the adenoma-carcinoma sequence. Ki-67, the current gold-standard marker of cellular proliferation, is a cell cycle protein that may lack sensitivity in demonstrating altered mucosal crypt cell dynamics. Minichromosome maintenance protein 2 (MCM2) has a specific role in DNA replication and has been proposed as a new marker for screening for colorectal cancer.
To compare the expression of Ki-67 with that of MCM2 in colorectal mucosa associated with colorectal cancer.
Ki-67 and MCM2 immunostaining was performed on serial sections taken from formalin-fixed, paraffin-embedded specimens. Labelling indices were calculated by counting the proportion of positively stained nuclei in representative areas of adenocarcinoma, and in equivalent superficial, middle and basal crypt compartments of mucosa sampled 1 cm from tumour (Ca1) and 10 cm from tumour (Ca10).
Specimens were obtained from 43 patients (27 adenocarcinoma, 16 no-cancer controls). Most nuclei in specimens of adenocarcinoma stained positively for MCM2 and Ki-67. In Ca1 and Ca10 samples, significantly greater staining of MCM2 than Ki-67 was seen in all crypt compartments. Receiver operator characteristic curve analysis suggested that proliferation changes (assessed by either MCM2 or Ki-67 staining) in Ca10, but not in Ca1, mucosa significantly predicted origin from a carcinoma-associated colon.
MCM2 was more sensitive than Ki-67 in identifying colorectal mucosal proliferation. Increased proliferation (assessed by either MCM2 or Ki-67 staining) in mucosa at 10 cm, but not at 1 cm, from carcinoma significantly predicted origin from a carcinoma-associated colon.
在腺瘤-癌序列的早期，黏膜隐窝细胞增殖失控导致增生性场改变。Ki-67是目前细胞增殖的金标准标志物，它是一种细胞周期蛋白，在显示黏膜隐窝细胞动力学改变方面可能缺乏敏感性。微小染色体维持蛋白2（MCM2）在DNA复制中具有特定作用，已被提议作为结直肠癌筛查的新标志物。
比较Ki-67和MCM2在结直肠癌相关结直肠黏膜中的表达。
对福尔马林固定、石蜡包埋标本的连续切片进行Ki-67和MCM2免疫染色。通过计数腺癌代表性区域以及距肿瘤1 cm（Ca1）和距肿瘤10 cm（Ca10）处黏膜的等效浅表、中间和基底隐窝区中阳性染色细胞核的比例来计算标记指数。
从43例患者（27例腺癌，16例非癌对照）获取标本。腺癌标本中的大多数细胞核MCM2和Ki-67染色呈阳性。在Ca1和Ca10样本中，所有隐窝区MCM2染色均显著强于Ki-67染色。受试者工作特征曲线分析表明，Ca10而非Ca1黏膜中的增殖变化（通过MCM2或Ki-67染色评估）显著预测了癌相关结肠的起源。
在识别结直肠黏膜增殖方面，MCM2比Ki-67更敏感。距癌10 cm而非1 cm处黏膜的增殖增加（通过MCM2或Ki-67染色评估）显著预测了癌相关结肠的起源。
