Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer
Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer
复制标题
DOI：
10.1200/jco.2005.04.1822
复制
发表时间：
2006-04-20
影响因子：
45.3
通讯作者：
Keilholz, U
中科院分区：
文献类型：
--
作者：
Ghadjar, P;Coupland, SE;Keilholz, U
目的：肝是结直肠癌（CRC）转移的主要器官。趋化因子受体CCR 6在T细胞亚群上表达，并与它们向肝脏的迁移有关。本研究分析了原发性结直肠癌和肝转移表达的CCR 6之间的可能关联。Patients and MethodsCCR 6表达水平通过免疫组织化学方法在64例结直肠癌原发肿瘤标本中进行了评价。64名患者中有24名患有同步肝转移。免疫染色的评价通过视觉评估进行半定量，并通过数字图像分析（DIA）进行定量。结果64例原发性肝癌组织中均有CCR 6的表达，21例（33%）呈弱阳性，32例（50%）呈中等阳性，11例（17%）呈强阳性。通过DIA进行的定量评估显示CCR 6值的差异高达5个对数。与邻近的结肠上皮细胞相比，肿瘤细胞中的CCR 6染色显著更强（P < .0005）。控制年龄、性别、肿瘤分期、淋巴结状态、病理分级和术前癌胚抗原水平的多元逻辑回归分析显示，原发肿瘤中CCR 6染色与肝转移的存在独立相关（优势比= 2.1; P = 0.002）的患者结论CCR 6在原发性结直肠癌和同时性肝转移中的表达水平可能与其配体的表达水平有关。转移到了肝脏因此，CCR 6可能是特异性治疗干预的潜在靶点。
PurposeThe liver is the primary organ of metastasis in colorectal cancer (CRC). Chemokine receptor CCR6 is expressed on a subset of T cells and is associated with their migration into the liver. This study was performed to analyze a possible association between CCR6 expressed by primary CRC and liver metastases.Patients and MethodsCCR6 expression levels were evaluated by immunohistology in 64 CRC primary tumor specimens. Twenty-four of 64 patients had synchronous liver metastases. Evaluation of immunostaining was performed semiquantitatively by visual assessment and quantitatively by digital image analysis (DIA). Multiple logistic regression analysis was performed to assess relevant parameters for liver metastases.ResultsCCR6 expression was verified in all 64 primary tumor specimens with considerable variations in intensity; 21 tumors (33%) demonstrated weak CCR6 staining, 32 (50%) demonstrated intermediate staining, and 11 (17%) demonstrated strong staining. Quantitative assessment by DIA showed an up to 5-log difference in CCR6 values. CCR6 staining was significantly stronger in tumor cells compared with adjacent colon epithelial cells (P < .0005). Multiple logistic regression analysis, controlling for age, sex, tumor stage, nodal status, pathologic grade, and preoperative carcinoembryonic antigen levels, revealed that CCR6 staining in the primary tumor was independently associated with the presence of liver metastases (odds ratio = 2.1; P = .002).ConclusionThe association between expression level of CCR6 in primary CRC and synchronous liver metastases suggests that CCR6 and its ligand may be involved in the metastatic spread to the liver. Therefore, CCR6 may be a potential target for specific therapeutic interventions.