Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece.
Dig Dis Sci. 2011 Mar;56(3):777-85. doi: 10.1007/s10620-010-1348-5. Epub 2010 Aug 6.
Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful biomarkers for cancer screening, surveillance and prognosis. The aim of the present study was to evaluate the clinical significance of MCM-2 and MCM-5 expression in gastric adenocarcinoma in comparison with Ki-67 proliferative marker.
MCM-2, MCM-5 and Ki-67 expression was assessed immunohistochemically in 66 tumoral samples of gastric adenocarcinoma patients and was statistically analyzed in relation to clinicopathological characteristics and patient survival.
MCM-2 expression did not show significant associations with any clinicopathological parameters, while Ki-67 expression was merely significantly associated with tumor size (P = 0.0150). MCM-2 and Ki-67 expression were more frequently in intestinal (median values: 67.5 and 60%) compared to diffuse-type (median values: 60 and 45%) gastric adenocarcinoma cases without though reaching statistical significance (P > 0.05). MCM-5 expression was significantly associated with tumor size (P = 0.0295), presence of lymph node metastases (P = 0.0216) and tumor histopathological stage (P = 0.0098). Patients presenting high MCM-5 expression had significantly shorter survival times (log-rank test, P = 0.0042), whereas neither MCM-2 nor Ki-67 expression showed significant prognostic value (log-rank test, P = 0.9618 and P = 0.7174, respectively). In multivariate analysis, patient age, histopathological stage and grade of differentiation, but not MCM-5 expression, were identified as independent prognostic factors (Cox regression analysis, P = 0.0097, P = 0.0195, P = 0.0035 and P = 0.3245, respectively).
The present study showed that MCM-5 expression was associated with clinicopathological parameters in gastric adenocarcinoma. However, further studies highlighting the distinct impact of the two histopathological types, intestinal and diffuse, are warranted to delineate whether MCMs could be used as diagnostic and prognostic markers in gastric neoplasia.
微小染色体维持（MCM）蛋白是 DNA 复制的必需组成部分，与细胞增殖有关，可作为癌症筛查、监测和预后的有用生物标志物。本研究旨在评估 MCM-2 和 MCM-5 在胃腺癌中的表达与 Ki-67 增殖标记物的临床意义。
采用免疫组织化学法检测 66 例胃腺癌患者肿瘤组织中 MCM-2、MCM-5 和 Ki-67 的表达，并分析其与临床病理特征及患者生存的关系。
MCM-2 表达与任何临床病理参数均无显著相关性，而 Ki-67 表达仅与肿瘤大小显著相关（P = 0.0150）。肠型（中位数 67.5%）胃腺癌中 MCM-2 和 Ki-67 的表达较弥漫型（中位数 60%）更为常见，但差异无统计学意义（P > 0.05）。MCM-5 表达与肿瘤大小（P = 0.0295）、淋巴结转移（P = 0.0216）和肿瘤组织学分期（P = 0.0098）显著相关。高 MCM-5 表达的患者生存时间明显缩短（log-rank 检验，P = 0.0042），而 MCM-2 和 Ki-67 的表达均无显著的预后价值（log-rank 检验，P = 0.9618 和 P = 0.7174）。多因素分析显示，患者年龄、组织学分期和分化程度，但不是 MCM-5 表达，是独立的预后因素（Cox 回归分析，P = 0.0097、P = 0.0195、P = 0.0035 和 P = 0.3245）。
本研究表明，MCM-5 表达与胃腺癌的临床病理参数相关。然而，需要进一步的研究来强调肠型和弥漫型两种组织学类型的不同影响，以确定 MCM 是否可以作为胃肿瘤的诊断和预后标志物。
