Loss of lamin A/C expression in stage II and III colon cancer is associated with disease recurrence
Loss of lamin A/C expression in stage II and III colon cancer is associated with disease recurrence
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DOI：
10.1016/j.ejca.2011.04.025
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发表时间：
2011-08-01
影响因子：
8.4
通讯作者：
Meijer, G. A.
中科院分区：
文献类型：
--
作者：
Belt, E. J. Th.;Fijneman, R. J. A.;Meijer, G. A.
研究目的：已观察到核层蛋白LMNA(LMNA)在几种人类恶性肿瘤中丢失。本研究旨在探讨LMNA在结肠癌患者中的表达与临床预后的关系。患者和方法：收集370例II期和III期结肠癌患者的临床病理资料和福尔马林固定的石蜡包埋组织。构建组织芯片，层蛋白A/C染色，并在显微镜下进行评估。结果：LMNA在17.8%的结肠癌中低水平表达，在LMNA低表达的II、III期结肠癌患者中有45.5%的患者复发，而在LMNA高表达的结肠癌患者中有29.6%的患者复发(p=0.01)。对于II期患者，LMNA低表达肿瘤的复发率为35.7%，而LMNA高表达肿瘤的复发率为20.3%(p=0.03)。微卫星稳定(MSS)肿瘤的LMNA低表达频率高于微卫星不稳定(MSI)肿瘤(21%对9.8%；p=0.05)。有趣的是，在没有接受辅助化疗的III期患者中，LMNA低表达和LMNA高表达的MSS肿瘤的复发率有显著差异(100%比37.8%；p<；0.01)，而接受辅助化疗的患者没有这种差异(46.7%比46.0%；p=0.96)。结论：这些数据表明LMNA的低表达与II和III期结肠癌患者疾病复发的增加有关，并提示这些患者可能特别受益于辅助化疗。(C)2011爱思唯尔有限公司。保留所有权利。
Aim of the study: Loss of the nuclear lamina protein lamin A/C (LMNA) has been observed in several human malignancies. The present study aimed to investigate associations between LMNA expression and clinical outcome in colon cancer patients.Patients and methods: Clinicopathological data and formalin-fixed paraffin embedded tissues were collected from 370 stage II and III colon cancer patients. Tissue microarrays were constructed, stained for lamin A/C and evaluated microscopically. Microsatellite instability status was determined for 318 tumours.Results: Low levels of LMNA expression were observed in 17.8% of colon tumours, with disease recurrence occurring in 45.5% of stage II and III colon cancer patients with LMNA-low expressing tumours compared to 29.6% of patients with LMNA-high expressing tumours (p = 0.01). For stage II patients, disease recurrence was observed for 35.7% of LMNA-low compared to 20.3% of LMNA-high expressing tumours (p = 0.03). Microsatellite stable (MSS) tumours exhibited more frequently low LMNA expression than microsatellite instable (MSI) tumours (21% versus 9.8%; p = 0.05). Interestingly, disease recurrence among LMNA-low and LMNA-high expressing MSS tumours varied significantly for stage III patients who had not received adjuvant chemotherapy (100% versus 37.8%; p < 0.01) while no such difference was observed for patients who received adjuvant chemotherapy (46.7% versus 46.0%; p = 0.96).Conclusion: These data indicate that low expression of LMNA is associated with an increased disease recurrence in stage II and III colon cancer patients, and suggest that these patients in particular may benefit from adjuvant chemotherapy. (C) 2011 Elsevier Ltd. All rights reserved.