Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with β-catenin
Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with β-catenin
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DOI：
10.1007/s00384-010-0903-z
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发表时间：
2010-05-01
影响因子：
2.8
通讯作者：
Huang, Qin
中科院分区：
文献类型：
--
作者：
Fan, Xiang-Shan;Wu, Hong-Yan;Huang, Qin
Lgr 5是G蛋白受体超家族的成员，最近被证明是肠分化细胞的干细胞标志物。它的过度表达已被证明在肝细胞癌，基底细胞癌，卵巢癌，但其潜在的机制知之甚少。本研究的目的是调查是否Lgr 5过度表达与人类结直肠癌的发生及其潜在的相关性beta-catenin.The研究进行了组织芯片，包括102结直肠癌（CRC; M：F = 55：47），18结肠腺瘤，和12结肠正常粘膜病例。用标准EnVision方法用抗Lgr 5、β-连环蛋白和p53抗原的一抗进行免疫染色。肿瘤细胞对每种抗体的免疫反应性由两名病理学家双盲半定量，数据用卡方和斯皮尔曼等级相关检验进行分析。对21例TMA阳性的结直肠癌组织中肿瘤中心和浸润边缘的Lgr 5表达进行了检测，并分析了它们之间Lgr 5表达的可能差异。Lgr 5仅见于正常结肠粘膜隐窝基底部的单个细胞，但在28%的正常结肠粘膜隐窝基底部的单个细胞中有较高的表达。（18例中有5例）腺瘤，54%（55/102，p = 0.016）CRC病例显著更高。在正常粘膜、腺瘤和结直肠癌中，β-连环蛋白表达分别为25%（3/12）、27%（5/18）和81%（83/102），而p53表达分别为0、0和40%（41/102）。在结直肠癌中，Lgr 5在女性中的表达比男性更强（p < 0.0001），并且与β-连环蛋白表达呈正相关（p < 0.001），但与患者的年龄、肿瘤大小、淋巴结状态、TNM分期和p53表达无关。结果提示，Lgr 5在大肠癌中的表达上调，尤其是在女性患者中，可能通过WNT/beta-catenin途径在大肠癌的发生发展中起重要作用，但与大肠癌的进展无关。
Lgr5 is a member of the G protein receptor super-family and was shown recently to be a stem cell marker for cells with intestinal differentiation. Its over-expression has been demonstrated in hepatocellular, basal cell carcinoma, and ovarian cancers but the underlying mechanisms are poorly understood. The aim of this study was to investigate if Lgr5 over-expression was correlated with human colorectal carcinogenesis and its potential correlation with beta-catenin.The study was carried out on a tissue microarray that consisted of 102 colorectal carcinomas (CRC; M:F = 55:47), 18 colon adenoma, and 12 colon normal mucosa cases. Immunostains were performed with the standard EnVision method with primary antibodies against Lgr5, beta-catenin, and p53 antigens. Immunoreactivity of neoplastic cells to each antibody was double-blindly semi-quantified by two pathologists and the data were analyzed with the Chi-square and Spearman rank correlation tests. Subsequently, expression of Lgr5 in tissue sections of tumor centre and invasive margins of 21 cases of CRC certified to be immunoreactive of Lgr5 in TMA were evaluated and possible differences of Lgr5 expression between them were analyzed.Lgr5 immunoreactivity was observed only in single cells in the base of normal colon mucosal crypts but high in 28% (five out of 18) adenomas, and significantly higher in 54% (55/102, p = 0.016) CRC cases. In normal mucosa, adenoma, and CRC, beta-catenin expression was seen in 25% (three out of 12), 27% (five out of 18), and 81% (83/102) cases, respectively, in contrast to 0, 0, and 40% (41/102) for p53 expression, respectively. In CRC, Lgr5 expression was more intense in women than men (p < 0.0001), and positively correlated with beta-catenin expression (p < 0.001), but not with patients' ages, tumor sizes, nodal status, TNM stages, and p53 expression. Different expression of Lgr5 between tumor centre and invasive margins was not found (p > 0.05).The results suggest that up-regulation of Lgr5 expression, especially in female patients, may play an important role in colorectal carcinogenesis, probably through the WNT/beta-catenin pathway, but not involve the progression of the CRC.