CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma

K. Slik, Riku Turkki, O. Carpén, S. Kurki, E. Korkeila, J. Sundström, T. Pellinen
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引用次数: 23

Abstract

Current risk factors in stage II colorectal carcinoma are insufficient to guide treatment decisions. Loss of CDX2 has been shown to associate with poor clinical outcome and predict benefit for adjuvant chemotherapy in stage II and III colorectal carcinoma. The prognostic relevance of CDX2 in stage II disease has not been sufficiently validated, especially in relation to clinical risk factors, such as microsatellite instability (MSI) status, BRAF mutation status, and tumor budding. In this study, we evaluated the protein expression of CDX2 in tumor center and front areas in a tissue microarrays material of stage II colorectal carcinoma patients (n=232). CDX2 expression showed a partial or total loss in respective areas in 8.6% and 10.9% of patient cases. Patients with loss of CDX2 had shorter disease-specific survival when scored independently either in tumor center or tumor front areas (log rank P=0.012; P=0.012). Loss of CDX2 predicted survival independently of other stage II risk factors, such as MSI status and BRAF mutation status, pT class, and tumor budding (hazard ratio=5.96, 95% confidence interval=1.55-22.95; hazard ratio=3.70, 95% confidence interval=1.30-10.56). Importantly, CDX2 loss predicted inferior survival only in patients with microsatellite stable, but not with MSI-high phenotype. Interestingly, CDX2 loss associated with low E-cadherin expression, tight junction disruption, and high expression of ezrin protein. The work demonstrates that loss of CDX2 is an independent risk factor of poor disease-specific survival in stage II colorectal carcinoma. Furthermore, the study suggests that CDX2 loss is linked with epithelial-to-mesenchymal transition independently of tumor budding.
伴有微卫星稳定表型的CDX2缺失预示着II期结直肠癌的不良临床预后
目前II期结直肠癌的危险因素不足以指导治疗决策。CDX2缺失已被证明与II期和III期结直肠癌辅助化疗的不良临床结果和预测获益相关。CDX2在II期疾病中的预后相关性尚未得到充分验证,特别是与临床危险因素,如微卫星不稳定性(MSI)状态、BRAF突变状态和肿瘤出芽有关。在这项研究中,我们评估了CDX2在II期结直肠癌患者(n=232)的组织微阵列材料中肿瘤中心和前部区域的蛋白表达。在8.6%和10.9%的患者中,CDX2在相应区域部分或全部表达缺失。CDX2缺失的患者在肿瘤中心或肿瘤前部单独评分时,疾病特异性生存期较短(log rank P=0.012;P = 0.012)。CDX2缺失独立于其他II期危险因素预测生存,如MSI状态和BRAF突变状态、pT类别和肿瘤出芽(风险比=5.96,95%可信区间=1.55-22.95;风险比=3.70,95%可信区间=1.30-10.56)。重要的是,CDX2缺失仅在微卫星稳定型患者中预测较差的生存期,而与msi高表型患者无关。有趣的是,CDX2缺失与E-cadherin低表达、紧密连接破坏和ezrin蛋白高表达相关。研究表明,CDX2的缺失是II期结直肠癌疾病特异性生存率差的独立危险因素。此外,该研究表明CDX2缺失与独立于肿瘤出芽的上皮到间质转化有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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