Clinicopathologic characteristics of high expression of Bmi-1 in esophageal adenocarcinoma and squamous cell carcinoma.
Clinicopathologic characteristics of high expression of Bmi-1 in esophageal adenocarcinoma and squamous cell carcinoma.
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DOI：
10.1186/1471-230x-12-146
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发表时间：
2012-10-18
影响因子：
2.4
通讯作者：
Zhou Z
中科院分区：
文献类型：
--
作者：
Choy B;Bandla S;Xia Y;Tan D;Pennathur A;Luketich JD;Godfrey TE;Peters JH;Sun J;Zhou Z
Bmi-1是多梳抑制复合物-1的关键调节组分，其高表达与许多实体和血液恶性肿瘤包括食管鳞状细胞癌相关。然而，关于Bmi-1在食管腺癌中的作用知之甚少。本研究旨在探讨Bmi-1在食管腺癌和鳞癌中的扩增和高表达及其与临床病理特征的关系。采用免疫组织化学（IHC）方法检测罗切斯特大学构建的组织芯片（TMA）中Bmi-1的蛋白表达水平。组织类型包括腺癌、鳞状细胞癌和癌前病变。收集患者的生存数据、人口统计学、组织学诊断和肿瘤分期数据。由两名病理学家对TMA载玻片上Bmi-1表达的强度（0-3）和百分比进行评分。使用AffyssSNP 6.0阵列分析了116例食管腺癌的基因组DNA拷贝数畸变。采用Fisher精确检验和Kaplan-Meier方法对数据进行分析。免疫组化结果显示，Bmi-1在几乎所有食管鳞状粘膜的基底层均有灶性表达，这与以往报道的其他干细胞相关器官的表达相似。从鳞状上皮（7%）、柱状细胞化生（22%）、Barrett食管（22%）到低度异型增生（45%）、高度异型增生（43%）和腺癌（37%），Bmi-1的高表达显著增加。Bmi-1表达水平与食管腺癌分化程度显著相关。在食管腺癌中，Bmi-1基因的扩增率很低（3%）。然而，Bmi-1高表达与食管腺癌和鳞状细胞癌的总生存率无关。本研究表明Bmi-1高表达与食管腺癌及癌前病变相关，提示Bmi-1在食管腺癌的早期癌变过程中起重要作用。
High expression of Bmi-1, a key regulatory component of the polycomb repressive complex-1, has been associated with many solid and hematologic malignancies including esophageal squamous cell carcinoma. However, little is known about the role of Bmi-1 in esophageal adenocarcinoma. The aim of this study is to investigate the amplification and high expression of Bmi-1 and the associated clinicopathologic characteristics in esophageal adenocarcinoma and squamous cell carcinoma. The protein expression level of Bmi-1 was detected by immunohistochemistry (IHC) from tissue microarrays (TMA) constructed at the University of Rochester from using tissues accrued between 1997 and 2005. Types of tissues included adenocarcinoma, squamous cell carcinoma and precancerous lesions. Patients’ survival data, demographics, histologic diagnoses and tumor staging data were collected. The intensity (0–3) and percentage of Bmi-1 expression on TMA slides were scored by two pathologists. Genomic DNA from 116 esophageal adenocarcinoma was analyzed for copy number aberrations using Affymetrix SNP 6.0 arrays. Fisher exact tests and Kaplan-Meier methods were used to analyze data. By IHC, Bmi-1 was focally expressed in the basal layers of almost all esophageal squamous mucosa, which was similar to previous reports in other organs related to stem cells. High Bmi-1 expression significantly increased from squamous epithelium (7%), columnar cell metaplasia (22%), Barrett’s esophagus (22%), to low- (45%) and high-grade dysplasia (43%) and adenocarcinoma (37%). The expression level of Bmi-1 was significantly associated with esophageal adenocarcinoma differentiation. In esophageal adenocarcinoma, Bmi-1 amplification was detected by DNA microarray in a low percentage (3%). However, high Bmi-1 expression did not show an association with overall survival in both esophageal adenocarcinoma and squamous cell carcinoma. This study demonstrates that high expression Bmi-1 is associated with esophageal adenocarcinoma and precancerous lesions, which implies that Bmi-1 plays an important role in early carcinogenesis in esophageal adenocarcinoma.