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Abstract：
Background: LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods: Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results: There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups (p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin (p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion: These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.
摘要：
背景:LGR5是结直肠癌(CRC)最重要的干细胞标志物之一。因为它增强了Wnt/β-连环蛋白信号传导。在CRC中腺瘤/癌序列期间发生的Wnt/β-连环蛋白信号传导的充分表征的失调使LGR5成为有希望的治疗靶标。我们评估了LGR5和β-catenin在正常结肠和肿瘤性病变中的免疫组织化学表达，并具有临床病理相关性。方法:选取50例正常黏膜组织块及临床资料,腺瘤12例，和30例CRC，其中切片被切割并重新检查,并且使用抗LGR5和抗β-连环蛋白进行免疫组织化学技术以测量染色密度。结果：与腺瘤和CRC样本相比，正常粘膜中LGR5无表达。关联分析表明，CRC标本比其他两组更可能具有强LGR5和β-catenin表达（分别为p=0.048和p<0.001）。高度发育不良腺瘤的标本更有可能表达LGR5和β-catenin的中强表达（分别为p=0.013和p=0.036）。相比之下,LGR5和β-catenin表达与分级和分期无统计学显著关联.结论：这些结果表明并支持LGR5作为散发性结直肠癌发生中癌症干细胞的潜在标志物的可能作用，以及根据免疫组织化学表达密度对LGR5和β-catenin在腺瘤性病变中的预后价值。LGR5在CRC中的潜在治疗作用基于其在发病机理中的作用被建议用于未来的研究。
