Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer.
Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer.
复制标题
DOI：
10.1158/1078-0432.ccr-09-0401
复制
发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Baba Y;Nosho K;Shima K;Freed E;Irahara N;Philips J;Meyerhardt JA;Hornick JL;Shivdasani RA;Fuchs CS;Ogino S
同源结构域转录因子CDX 2是胃肠道癌的一个相对特异的免疫组化标记。然而，还没有研究全面探讨CDX 2表达与结肠癌的临床，病理，预后和分子特征，包括微卫星不稳定性（MSI）和CpG岛甲基化表型（CIMP）之间的关系。利用621例结直肠癌的临床结果和分子数据，通过免疫组化在183例（29%）肿瘤中检测到CDX 2丢失。在多变量logistic回归分析中，CDX 2丢失与女性性别相关[比值比（OR）=3.32; p<0.0001]，CIMP高（OR=4.42; p=0.0003），高肿瘤分级（OR=2.69; p=0.0085），IV期疾病（OR=2.03; p=0.019），与LINE-1低甲基化成反比（下降30%; OR=0.33; p=0.0031），p53表达（OR=0.55; p=0.011）、β-连环蛋白活化（OR=0.60; p=0.037），但与体重指数、肿瘤位置、MSI、BRAF、KRAS、PIK 3CA、p21或考克斯-2无关。CDX 2丢失与患者生存率无关。然而，CDX 2丢失的预后影响似乎根据结直肠癌家族史而不同（P相互作用=0.0094）。在有结直肠癌家族史的患者中，CDX 2缺失与高总体死亡率相关[多变量风险比（HR）=2.40; 95%CI，1.28-4.51];在无结直肠癌家族史的患者中不存在这种相关性（多变量HR=0.97; 95%CI，0.66-1.41）。结直肠癌中的CDX 2缺失与女性性别、CIMP高、LINE-1高水平甲基化、高肿瘤分级和晚期独立相关。CDX 2缺失可能与有结直肠癌家族史的患者预后不良相关。
The homeodomain transcription factor CDX2 is a relatively specific immunohistochemical marker for gastrointestinal carcinoma. However, no study has comprehensively examined the relationship between CDX2 expression in colon cancer and clinical, pathologic, prognostic and molecular features, including microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Utilizing 621 colorectal cancers with clinical outcome and molecular data, CDX2 loss was detected in 183 (29%) tumors by immunohistochemistry. In multivariate logistic regression analysis, CDX2 loss was associated with female gender [odds ratio (OR)=3.32; p<0.0001], CIMP-high (OR=4.42; p=0.0003), high tumor grade (OR=2.69; p=0.0085), stage IV disease (OR=2.03; p=0.019), and inversely with LINE-1 hypomethylation (for a 30% decline; OR=0.33; p=0.0031), p53 expression (OR=0.55; p=0.011), β-catenin activation (OR=0.60; p=0.037), but not with body mass index, tumor location, MSI, BRAF, KRAS, PIK3CA, p21 or COX-2. CDX2 loss was not independently associated with patient survival. However, the prognostic effect of CDX2 loss appeared to differ according to family history of colorectal cancer (Pinteraction=0.0094). CDX2 loss was associated with high overall mortality [multivariate hazard ratio (HR)=2.40; 95% CI, 1.28–4.51] among patients with a family history of colorectal cancer; no such association was present (multivariate HR=0.97; 95% CI, 0.66–1.41) among patients without a family history of colorectal cancer. CDX2 loss in colorectal cancer is independently associated with female gender, CIMP-high, high-level LINE-1 methylation, high tumor grade, and advanced stage. CDX2 loss may be associated with poor prognosis among patients with a family history of colorectal cancer.