Department of Surgery, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
Eur J Cancer. 2011 Aug;47(12):1837-45. doi: 10.1016/j.ejca.2011.04.025. Epub 2011 May 27.
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.
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.
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).
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.
核纤层蛋白 A/C（LMNA）的缺失已在多种人类恶性肿瘤中观察到。本研究旨在探讨结肠癌患者中 LMNA 表达与临床结局的关系。
收集了 370 例 II 期和 III 期结肠癌患者的临床病理数据和福尔马林固定石蜡包埋组织。构建组织微阵列，对 LMNA 进行染色并进行显微镜评估。对 318 个肿瘤进行微卫星不稳定性状态的测定。
在 17.8%的结肠癌中观察到 LMNA 低表达，与 LMNA 高表达肿瘤患者相比，LMNA 低表达肿瘤患者的 II 期和 III 期结肠癌患者的疾病复发率分别为 45.5%和 29.6%（p=0.01）。对于 II 期患者，LMNA 低表达的疾病复发率为 35.7%，而 LMNA 高表达的肿瘤为 20.3%（p=0.03）。微卫星稳定（MSS）肿瘤的 LMNA 低表达频率明显高于微卫星不稳定（MSI）肿瘤（21%比 9.8%；p=0.05）。有趣的是，未接受辅助化疗的 III 期患者中，LMNA 低表达和 LMNA 高表达 MSS 肿瘤的疾病复发率差异显著（100%比 37.8%；p<0.01），而接受辅助化疗的患者则无差异（46.7%比 46.0%；p=0.96）。
这些数据表明，LMNA 低表达与 II 期和 III 期结肠癌患者的疾病复发增加相关，并表明这些患者尤其可能受益于辅助化疗。
