Demarez Céline, Hubert Catherine, Sempoux Christine, Lemaigre Frédéric P
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Division of Hepato-Biliary and Pancreatic Surgery, Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
PLoS One. 2016 Jun 9;11(6):e0157140. doi: 10.1371/journal.pone.0157140. eCollection 2016.
The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1β), Yes-associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR-135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria.
根据组织形态学标准定义的肿瘤细胞分化状态，是肝内胆管癌（ICC）患者生存的一个预后因素。为了强化形态学分化标准的价值，我们希望将组织病理学分化程度与分子胆管分化标志物以及先前已证实在ICC中失调的微小RNA的表达相关联。我们分析了一系列组织学上分类为高分化、中分化或低分化的肿瘤，并通过定量逆转录聚合酶链反应（qRT-PCR）和免疫染色研究了细胞角蛋白7、19和903（CK7、CK19、CK903）、SRY相关高迁移率族盒转录因子4和9（SOX4、SOX9）、骨桥蛋白（OPN）、肝细胞核因子-1β（HNF1β）、Yes相关蛋白（YAP）、上皮细胞粘附分子（EPCAM）、粘蛋白1（MUC1）和N-钙粘蛋白（NCAD）的表达，以及miR-31、miR-135b、miR-132、miR-200c、miR-221和miR-222的表达。出乎意料的是，除了SOX9和OPN的亚细胞定位外，这些分子标志物的表达水平与组织病理学分化程度之间未发现相关性。因此，我们的数据表明，在基于细胞分化标准研究ICC的进展和预后时需要谨慎。
