Three-dimensional analysis of extrahepatic cholangiocarcinoma and tumor budding.
Three-dimensional analysis of extrahepatic cholangiocarcinoma and tumor budding.
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DOI：
10.1002/path.5474
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发表时间：
2020-08
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--
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组织透明化和显微镜技术的进步使得在三维（3D）中研究人类疾病成为可能。已知高级别肿瘤出芽与各种癌症的不良预后相关;然而，对肿瘤出芽的3D结构知之甚少。利用组织透明技术，我们分析了31例肝外胆管癌中肿瘤出芽和E-钙粘蛋白表达的三维结构。从手术切除的肿瘤组织中共获得31个厚平板（最大5 mm），包括27个肝门和4个远端胆管癌。腺癌28例，未分化癌3例。清除后，组织免疫标记的抗体细胞角蛋白19和E-钙粘蛋白，然后可视化使用光片和共聚焦激光扫描显微镜。使用标准病理学标准在苏木精和伊红染色切片（2D）中评价肿瘤出芽。在31例癌症中，13例显示低级别肿瘤出芽，18例显示高级别肿瘤出芽。首先，3D分析显示，腺癌的肿瘤芽中的肿瘤细胞通常不是单独的细胞岛，而是与主肿瘤连接的衰减突起的尖端。第二，低级别肿瘤出芽的腺癌主要由仅在外周局灶性形成索状的小管组成。相比之下，高级别肿瘤出芽的腺癌主要在肿瘤的中心和周围形成索状结构。第三，具有低级别肿瘤出芽的腺癌的特征在于具有很少分支的一些短突起，而具有高级别肿瘤出芽的腺癌的特征在于具有更多分支的较长突起。最后，免疫标记的E-钙粘蛋白是较强的腺癌的中心，但在突起的尖端减少。高级别肿瘤出芽的突起中的E-钙粘蛋白丢失比低级别肿瘤出芽的突起中的E-钙粘蛋白丢失更广泛。我们的研究结果表明，肿瘤芽，如在2D中看到的，实际上是从主肿瘤延伸的衰减但连续的突起的横截面。
Advances in tissue clearing and microscopy make it possible to study human diseases in three dimensions (3D). High-grade tumor budding is known to be associated with poor prognosis in various cancers; however, little is known about the 3D architecture of tumor budding. Using tissue clearing, we analyzed the 3D structure of tumor budding and E-cadherin expression in 31 extrahepatic cholangiocarcinomas. A total of 31 thick slabs (up to 5 mm) were harvested from surgically resected tumor tissue, including 27 hilar and 4 distal cholangiocarcinomas. Twenty-eight cases were adenocarcinoma, and three were undifferentiated carcinoma. After clearing, the tissues were immunolabeled with antibodies to cytokeratin 19 and to E-cadherin, and then visualized using light-sheet and confocal laser scanning microscopy. Tumor budding was evaluated in hematoxylin and eosin–stained sections (2D) using standard pathological criteria. Of the 31 cancers, 13 showed low-grade tumor budding and 18 showed high-grade tumor budding. First, 3D analysis revealed that the neoplastic cells in tumor buds of adenocarcinoma were typically not individual islands of cells, but rather tips of attenuated protrusions connected to the main tumor. Second, adenocarcinomas with low-grade tumor budding were composed predominantly of tubules that only focally form cords at the periphery. By contrast, adenocarcinomas with high-grade tumor budding predominantly formed cords in both centers and peripheries of the tumors. Third, adenocarcinoma with low-grade tumor budding was characterized by a few short protrusions with few branches, whereas adenocarcinoma with high-grade tumor budding was characterized by longer protrusions with more branching. Finally, immunolabeling of E-cadherin was stronger in the center of the adenocarcinoma but decreased at the tips of protrusions. E-cadherin loss was more extensive in the protrusions of high-grade tumor budding than in the protrusions of low-grade tumor budding. Our findings suggest that tumor buds as seen in 2D are, in fact, cross-sections of attenuated but contiguous protrusions extending from the main tumor.
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影响因子：
64.5
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
通讯作者：
Ewald AJ
影响因子：
3.3
作者：
Olsen, Stephen;Jin, Linda;Nalbantoglu, ILKe
通讯作者：
Nalbantoglu, ILKe
影响因子：
7.3
作者：
Bronsert, P.;Enderle-Ammour, K.;Wellner, U. F.
通讯作者：
Wellner, U. F.
影响因子：
2.1
作者：
Lorenzo Soriano, Laura;Ordaz Jurado, Guzman;Ramos Soler, David
通讯作者：
Ramos Soler, David
影响因子：
6
作者：
Noe, Michael;Rezaee, Neda;Hruban, Ralph H.
通讯作者：
Hruban, Ralph H.