Lgr5, an intestinal stem cell marker, is abnormally expressed in Barrett's esophagus and esophageal adenocarcinoma
Lgr5, an intestinal stem cell marker, is abnormally expressed in Barrett's esophagus and esophageal adenocarcinoma
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DOI：
10.1111/j.1442-2050.2009.00979.x
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发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
Mashimo, H.
中科院分区：
文献类型：
--
作者：
Becker, L.;Huang, Q.;Mashimo, H.
Lgr 5（富含亮氨酸重复序列的G蛋白偶联受体5）是最近发现的肠干细胞标志物，在包括巴雷特食管（BE）在内的癌前病变和包括结肠癌、卵巢癌和肝细胞癌在内的癌症中表达。最近还发现它在从结肠癌制备的肿瘤球中表达，这表明它可能作为癌症干细胞标记物。我们试图检查Lgr 5作为BE相关瘤形成的生物标志物。使用标准的免疫组织化学，我们进行了81例食管标本（53例活检标本和28例手术切除）代表BE，BE相关的异型增生，食管腺癌（EAC）的免疫染色。基于免疫染色强度和阳性细胞百分比对每种免疫染色进行评分。对24例EAC病例进行了生存分析，包括表达评分和其他临床病理变量。我们发现，Lgr 5的表达在70%的BE病例和90%至100%的晚期异型增生病变和EAC中检测到。表达强度在高度异型增生和EAC中显著高于BE。在EAC中，高Lgr 5表达评分（>= 5）与较差的生存率相关，与分期、年龄和新辅助/辅助治疗无关（P = 0.03）。我们的研究结果表明，Lgr 5具有潜在的效用作为BE相关的发育不良和EAC的生物标志物。
P>Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5), a recently discovered intestinal stem cell marker, is expressed in premalignant lesions including Barrett's esophagus (BE) and cancers including colon cancer, ovarian cancer, and hepatocellular carcinoma. It was also recently found to be expressed in tumor spheres prepared from colon cancer, suggesting that it will likely serve as a cancer stem cell marker. We sought to examine Lgr5 as a biomarker in BE-associated neoplasia. Using standard immunohistochemistry, we performed immunostaining on 81 esophageal specimens (53 biopsy specimens and 28 surgical resections) representing BE, BE-associated dysplasia, and esophageal adenocarcinoma (EAC). Each immunostain was scored based on intensity of immunostaining and percentage of positive cells. For 24 EAC cases, survival analysis was performed with expression scores and other clinicopathological variables. We found that Lgr5 expression was detected in 70% of BE cases and between 90 and 100% of advanced dysplastic lesions and EAC. The intensity of expression was significantly higher in high-grade dysplasia and EAC than BE. In EAC, high Lgr5 expression scores (>= 5) were associated with worse survival, independent of stage, age, and neoadjuvant/adjuvant therapy (P = 0.03). Our findings suggest that Lgr5 has potential utility as a biomarker for BE-associated dysplasia and EAC.