EphB2 is a prognostic factor in colorectal cancer
EphB2 is a prognostic factor in colorectal cancer
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DOI：
10.1158/1078-0432.ccr-05-0143
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发表时间：
2005-07-15
影响因子：
11.5
通讯作者：
Koeppen, H
中科院分区：
文献类型：
--
作者：
Jubb, AM;Zhong, F;Koeppen, H
EphB2是一种肾上腺素配体的受体酪氨酸激酶，在结直肠癌中表达，已被认为是免疫偶联治疗的靶点。本研究的目的是对EphB2在正常和肿瘤大肠组织中的表达进行详细的组织学分析。此外，我们试图评估EphB2的表达作为结直肠癌的预后因素。应用免疫组织化学方法检测EphB2在正常结肠(n=28)、结直肠癌细胞系(n=20)、结直肠腺瘤(n=148)、原发癌(n=28)和转移癌(n=39)中的表达。此外，一系列具有结果数据的原发癌症和匹配的正常组织(n=342)在组织芯片中被描绘出来。用免疫组织化学方法检测EphB2在整个序列中的表达强度，用原位杂交法检测EphB2在亚组中的表达强度。在回溯性亚组分析中，总体生存率和无复发生存率与EphB2蛋白表达相关。EphB2在结直肠癌发生的各个阶段均有表达，包括所有正常腺体的基底部、77%的腺瘤、82%的原发癌和%的转移灶。虽然在腺瘤中观察到均匀的表达，但在大多数恶性病变中，染色模式是局灶性的(平均25%)。EphB2表达为2+的患者总体生存时间显著延长：平均生存期为2,514天对1,044天；风险比为0.45；95%可信区间为0.18-0.95(P=0.035)。综上所述，EphB2在正常腺体、结直肠腺瘤、原发癌和转移瘤中均有表达。EphB2的高水平表达与结直肠癌的平均生存期较长有关。
A receptor tyrosine kinase for ephrin ligands, EphB2 is expressed in colorectal cancer and has been proposed as a target for immunoconjugate therapy. The aim of this study was to perform a detailed histologic analysis of EphB2 expression in normal and neoplastic colorectal tissues. In addition, we sought to evaluate EphB2 expression as a prognostic factor in colorectal cancer. Expression of EphB2 was examined in normal colon (n = 28),colorectal cell lines (n = 20), colorectal adenomas (n = 148), primary cancers (n = 28), and metastases (n = 39) using immunohistochemistry. In addition, a series of primary cancers and matched normal (n = 342) with outcome data were profiled in tissue microarrays. The intensity of EphB2 expression was assessed in the entire series by immunohistochemistry, and in a subset by in situ hybridization. Overall survival and recurrence-free survival were correlated with EphB2 protein expression in retrospective subset analyses. Epithelial EphB2 expression was shown at all stages of colorectal tumorigenesis, including the base of all normal crypts, 77% of adenomas, 82% of primary cancers, and 64% of metastases. Although homogeneous expression was observed in adenomas, the pattern of staining was focal (mean 25%) in most malignant lesions. Patients whose tumor stained 2+ for EphB2 expression (versus 0/1 +) exhibited significantly prolonged overall survival: mean duration of survival, 2,514 versus 1,044 days; hazard ratio, 0.45; 95% confidence interval, 0.18 to 0.95 (P = 0.035). In summary, EphB2 is expressed in normal crypts, colorectal adenomas, primary cancers, and metastases. High levels of EphB2 expression are associated with a longer mean duration of survival in colorectal cancer.