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胰腺实性假乳头状肿瘤中细胞粘附分子复合物的缺失。

Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas.

作者信息

Tang Wendell W, Stelter Arwen A, French Samuel, Shen Steven, Qiu Suimin, Venegas Rose, Wen Julie, Wang Hui-Qun, Xie Jingwu

机构信息

Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.

出版信息

Mod Pathol. 2007 May;20(5):509-13. doi: 10.1038/modpathol.3800764. Epub 2007 Mar 2.

Abstract

Solid pseudopapillary tumor of pancreas (SPT) is a rare neoplasm that occurs most often in young females with the two distinct features, the 'solid-cystic' gross appearance, and the 'solid-pseudopapillary' microscopic pattern. It has been reported that almost all SPT tumors contain a mutation in the beta-catenin gene; however, the histogenetic origin of this tumor remains largely a mystery. E-cadherin is a cell adhesion molecule that links to catenins to form cell adhesion junctions, which is associated with the cytoskeleton formation. In this study, we examined the expression of E-cadherin and beta-catenin from SPT in an attempt to determine the molecular basis for the unusual morphology of this tumor. Nine cases of SPT were retrieved from Surgical Pathologic Archives of three institutions, including one male and eight females. H&E slides of each case were reviewed to confirm the diagnosis. The beta-catenin gene was sequenced in one case. E-cadherin and beta-catenin immunostains, were performed on all nine cases. Sequencing analysis on one case showed a point mutation of the beta-catenin gene, confirming previous findings that almost all SPT tumors contain mutation in the beta-catenin gene. Immunostains showed that, in both solid and pseudopapillary areas, all the tumor cells lost expression of E-cadherin, and beta-catenin nuclear expression was observed in all cases. Our findings suggest that loss of cytoplasmic beta-catenin protein in the cell adhesion complex due to beta-catenin gene mutation, results in instability of the complex, loss of E-cadherin in cell membrane, and eventually dissociation of the tumor cells to form the pseudopapillary pattern.

摘要

胰腺实性假乳头状瘤(SPT)是一种罕见的肿瘤,最常发生于年轻女性,具有两个显著特征,即大体外观为“实性-囊性”,镜下形态为“实性-假乳头状”。据报道,几乎所有SPT肿瘤的β-连环蛋白基因都存在突变;然而,这种肿瘤的组织发生起源在很大程度上仍是个谜。E-钙黏蛋白是一种细胞黏附分子,它与连环蛋白相连形成细胞黏附连接,与细胞骨架的形成有关。在本研究中,我们检测了SPT中E-钙黏蛋白和β-连环蛋白的表达,试图确定这种肿瘤异常形态的分子基础。从三个机构的外科病理档案中检索到9例SPT病例,其中男性1例,女性8例。对每例病例的苏木精-伊红(H&E)切片进行复查以确诊。对其中1例进行了β-连环蛋白基因测序。对所有9例病例进行了E-钙黏蛋白和β-连环蛋白免疫染色。对1例病例的测序分析显示β-连环蛋白基因存在点突变,证实了先前的发现,即几乎所有SPT肿瘤的β-连环蛋白基因都存在突变。免疫染色显示,在实性和假乳头状区域,所有肿瘤细胞均失去E-钙黏蛋白表达,所有病例均观察到β-连环蛋白核表达。我们的研究结果表明,β-连环蛋白基因突变导致细胞黏附复合物中细胞质β-连环蛋白蛋白缺失,导致复合物不稳定,细胞膜上E-钙黏蛋白丢失,最终肿瘤细胞解离形成假乳头状结构。

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