Loss of Cdx2 expression In pri ary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer
Loss of Cdx2 expression In pri ary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer
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DOI：
10.3389/fonc.2013.00265
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Zlobec, Intl
中科院分区：
文献类型：
--
作者：
Dawson, Heather;Koelzer, Viktor H.;Zlobec, Intl
背景资料：据推测，大约20%的结直肠癌是由以BRAF突变、高水平CpG岛甲基化表型和微卫星不稳定性/错配修复（MMR）缺陷为特征的“锯齿状途径”引起的。MMR缺陷型癌症显示Cdx 2（一种同源域转录因子）的频繁丢失。在这里，我们确定的预测价值Cdx 2表达MMR缺陷和调查之间的表达变化的原发癌和匹配的淋巴结transfactor.Methods：免疫组化Cdx 2，M1 h1，Msh 2，Msh 6，和Pms 2进行全组织切片从201例原发性结直肠癌和59例匹配的淋巴结转移。受试者工作特征曲线分析和曲线下面积（AUC）进行了调查; Cdx 2与临床病理特征和患者survivalwascarried.Results：Cdx 2表达的损失与较高的肿瘤分级（p= 0.0002），先进的pT（p= 0.0166），和神经浸润（p= 0.0228）。在单变量（p= 0.0145）和多变量[p= 0.0427; HR（95%CI）：0.58（0.34-0.98）]分析中，Cdx 2丢失是不利的预后因素。区分MMR熟练型和缺陷型癌症的准确度（AUC）为87% [OR（95%CI）：0.96（0.95-0.98）; p < 0.0001]。MMR缺陷的特异性和阴性预测值分别为99.1%和96.3%。174名患者患有MMR熟练的癌症，其中60名（34.5%）显示Cdx 2丢失。转移瘤中Cdx 2丢失与MMR缺陷相关（p
Background: Approximately 20% of all colorectal cancers are hypothesized to arise from the "serrated pathway" characterized by mutation in BRAF, high-level CpG Island Methylator Phenotype, and microsatellite instability/mismatch repair (MMR)-deficiency. MMRdeficient cancers show frequent losses of Cdx2, a homeodomain transcription factor. Here, we determine the predictive value of Cdx2 expression for MMR-deficiency and investigate changes in expression between primary cancers and matched lymph node metastases.Methods: lmmunohistochemistry for Cdx2, M1h1, Msh2, Msh6, and Pms2 was performed on whole tissue sections from 201 patients with primary colorectal cancer and 59 cases of matched lymph node metastases. Receiver operating characteristic curve analysis and Area under the Curve (AUC) were investigated; association of Cdx2 with clinicopathological features and patient survival was carried out.Results: Loss of Cdx2 expression was associated with higher tumor grade (p= 0.0002), advanced pT (p= 0.0166), and perineural invasion (p= 0.0228). Cdx2 loss was an unfavorable prognostic factor in univariate (p= 0.0145) and multivariate [p= 0.0427; HR (95% CI): 0.58 (0.34-0.98)] analysis. The accuracy (AUC) for discriminating MMR-proficient and deficient cancers was 87% [OR (95% CI): 0.96 (0.95-0.98); p < 0.0001]. Specificity and negative predictive value for MMR-deficiency was 99.1 and 96.3%. One hundred and seventy-four patients had MMR-proficient cancers, of which 60 (34.5%) showed Cdx2 loss. Cdx2 loss in metastases was related to MMR-deficiency (p