Choy Bonnie, LaLonde Amy, Que Jianwen, Wu Tongtong, Zhou Zhongren
Department of Pathology, University of Chicago, Chicago, IL 60637.
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642.
Hum Pathol. 2016 Nov;57:126-135. doi: 10.1016/j.humpath.2016.07.013. Epub 2016 Jul 29.
Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and precancerous lesions. The mean percentage of MCM4, MCM7, and Ki-67 expression increased from squamous epithelium (5.5%, 7.3%, and 5.9%, respectively), to columnar cell metaplasia (11.2, 13.5%, and 3.4%), Barrett's esophagus (27.7%, 35.3%, and 8.3%), low-grade dysplasia (42.6%, 52.2%, and 12.9%), high-grade dysplasia (63.2%, 77.7%, and 29.6%), adenocarcinoma (61.3%, 75.5%, and 24.5%), and squamous cell carcinoma (74.1, 85.4%, and 36.3%). The percentages of MCM4 and MCM7 expression were significantly higher than Ki-67 expression. Using univariate analysis we found a high percentage of MCM4 expression (>70%) to be significantly associated with lymph node metastasis and shorter survival in the adenocarcinoma group. We also demonstrated the percentage of MCM4 and MCM7 expression to be significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma and precancerous lesions. MCM4 and MCM7 may serve as more sensitive proliferative markers for the evaluation of esophageal lesions.
微小染色体维持（MCM）蛋白是DNA复制的参与者，在确定肿瘤内增殖分数方面可能比增殖标志物Ki-67更准确。我们的研究调查了食管腺癌、鳞状细胞癌及癌前病变中MCM4和MCM7表达与Ki-67、Bmi1和细胞周期蛋白E表达之间的相关性。在食管癌及癌前病变中，MCM4和MCM7表达与Ki-67和Bmi1表达具有相似的分布。MCM4、MCM7和Ki-67表达的平均百分比从鳞状上皮（分别为5.5%、7.3%和5.9%），增加到柱状上皮化生（11.2%、13.5%和3.4%）、巴雷特食管（27.7%、35.3%和8.3%）、低级别异型增生（42.6%、52.2%和12.9%）、高级别异型增生（63.2%、77.7%和29.6%）、腺癌（61.3%、75.5%和24.5%）以及鳞状细胞癌（74.1%、85.4%和36.3%）。MCM4和MCM7表达的百分比显著高于Ki-67表达。单因素分析发现，腺癌组中高百分比的MCM4表达（>70%）与淋巴结转移及较短生存期显著相关。我们还证明，在食管癌及癌前病变中，MCM4和MCM7表达的百分比与Ki-67、Bmi1和细胞周期蛋白E表达显著相关。MCM4和MCM7可能作为评估食管病变更敏感的增殖标志物。
