Overexpression of Claudin proteins in esophageal adenocarcinoma and its precursor lesions
Overexpression of Claudin proteins in esophageal adenocarcinoma and its precursor lesions
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DOI：
10.1097/01.pai.0000151933.04800.1c
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发表时间：
2006-03-01
影响因子：
1.6
通讯作者：
Berg, KD
中科院分区：
文献类型：
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作者：
Montgomery, E;Mamelak, AJ;Berg, KD
Claudius 是紧密连接的组成部分，对于细胞间屏障和细胞极性很重要。作者使用 Affymetrix U-133 寡核苷酸微阵列和免疫组织化学 (IHC) 确定了胃腺癌中 Claudius 3、4 和 7 的上调。虽然正常胃粘膜缺乏 Claudin 3、4 和 7 表达，但肠化生和不典型增生则显示这些蛋白。作者假设 Claudius 在巴雷特食管 (BE)/腺癌中也会同样过度表达。通过 Affymetrix U-133 微阵列分析了三例食管腺癌、一例 BE 病例和三例正常食管中的 Claudius 3、4 和 7 基因表达。使用由食管切除标本构建的组织微阵列进行 IHC 验证，其中包括鳞状癌（44 例）、胃癌（40 例）和非不典型增生 BE（16 例）、低度和高度不典型增生（16 例和 26 例）、腺癌（58 例）和淋巴结转移（27 例）。 IHC 染色半定量评分（0 + 至 4 +）。通过微阵列分析，与正常食管相比，Claudin 3 的 mRNA 表达显着增加（约 100 倍）。 Claudius 4 和 7 略有增加（2.2 倍和 1.3 倍）。通过 IHC，大多数 (> 95%) 正常鳞状或胃组织中 Claudin 3 表达为 I +，而在超过 80% 的高度不典型增生、腺癌和转移标本中，Claudin 3 表达为 2+ 至 4+。在大多数鳞状和胃粘膜 (> 90%) 中，Claudin 4 蛋白表达为 2+ 或更低，但在 BE、低度和高度不典型增生、腺癌和转移标本 (> 90%) 中，表达为 3 + 或 4+。 Claudin 7 在鳞状和胃粘膜中表达最少，但在 BE 和低度不典型增生中表达较强（3 + 至 4+）。在高度不典型增生、腺癌和转移瘤中，Claudin 7 的强度较低，60% 至 70% 染色为 3 + 或 4 +，30% 至 40% 染色为弱（1 + 或 2 +）。研究结果表明，Claudin 蛋白的改变是肿瘤发生的早期事件，可能为食管腺癌及其相关疾病的诊断和定向治疗提供靶点。 前体。
Claudius are components of tight junctions important in intercellular barriers and cell polarity. The authors identified upregulation of Claudius 3, 4, and 7 in gastric adenocarcinoma using Affymetrix U-133 oligonucleotide microarrays and immunohistochemistry (IHC). While normal gastric mucosa lacked Claudin 3, 4, and 7 expression, intestinal metaplasia and dysplasia showed these proteins. The authors hypothesized that Claudius would be similarly overexpressed in Barrett's esophagus (BE)/adenocarcinoma. Claudius 3, 4, and 7 gene expression was analyzed by Affymetrix U-133 microarrays in three esophageal adenocarcinomas, one case of BE, and three normal esophagi. IHC validation was performed using tissue microarrays constructed from esophageal resection specimens containing squamous (44 cases), gastric (40 cases), and nondysplastic BE (16 cases), low-grade and high-grade dysplasia (16 and 26 cases), adenocarcinoma (58 cases), and nodal metastases (27 cases). IHC staining was scored semiquantitatively (0 + to 4 +). By microarray analysis, Claudin 3 showed a marked increase in mRNA expression compared with normal esophagus (approximately 100-fold). Claudius 4 and 7 were modestly increased (2.2- and 1.3-fold). By IHC, Claudin 3 expression was I + in most (> 95%) normal squamous or gastric tissues and 2+ to 4+ in more than 80% of high-grade dysplasia, adenocarcinoma, and metastases specimens. Claudin 4 protein expression was 2+ or less in most squamous and gastric mucosa (> 90%) but 3 + or 4+ in BE, low- and high-grade dysplasia, adenocarcinoma, and metastases specimens (> 90%). Claudin 7 expression was minimal in squamous and gastric mucosa but strong (3 + to 4+) in BE and low-grade dysplasia. In high-grade dysplasia, adenocarcinoma, and metastases, Claudin 7 was less intense, with 60% to 70% staining 3 + or 4 + and 30% to 40% staining weakly (1 + or 2 +), The findings suggest that alterations in Claudin proteins are an early event in tumorigenesis and may provide targets for diagnosis and directed therapy for esophageal adenocarcinoma and its precursors.