PMID- 31401234 OWN - NLM STAT- MEDLINE DCOM- 20200610 LR - 20200610 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 92 DP - 2019 Oct TI - The expression of gastrointestinal differentiation markers in extrahepatic cholangiocarcinoma: clinicopathological significance based on tumor location. PG - 91-100 LID - S0046-8177(19)30135-2 [pii] LID - 10.1016/j.humpath.2019.08.002 [doi] AB - The expression of gastrointestinal differentiation markers is associated with the tumorigenesis and prognosis of digestive cancers. However, little is known about the significance of gastrointestinal differentiation marker profiles in patients with extrahepatic cholangiocarcinoma (CCA), which is classified as perihilar and distal CCA. The purpose of this study was to clarify the role of gastrointestinal differentiation marker expression in extrahepatic CCA based on tumor location. We examined the expression of gastrointestinal differentiation markers in resected perihilar (n = 30) and distal (n = 54) CCAs based on the immunohistochemical expression of the following markers: MUC2, MUC5AC, MUC6, CD10, CDX-2, and cytokeratin 20. Expression scores were determined semiquantitatively based on the rate of positively stained cells. Furthermore, we performed hierarchical clustering of the CCAs based on the immunohistochemical expression scores to evaluate differences in the expression patterns of the 6 gastrointestinal differentiation markers. Consequently, perihilar and distal CCAs were stratified into 2 subgroups each. Among the perihilar CCAs, subgroup 1 was characterized by lower expression of MUC5AC and MUC6, a larger median tumor size, and a significantly worse prognosis compared with subgroup 2. Furthermore, the immunohistological subgroup (subgroup 1 versus 2) and TNM stage (stage III versus II) were independent predictors of patient survival. Among the distal CCAs, subgroup 1 was characterized by lower expression of MUC5AC compared with subgroup 2. We suggest that gastrointestinal differentiation marker profiles are useful for stratifying perihilar and distal CCAs. In addition, gastrointestinal differentiation markers play a crucial role in tumor development, particularly in perihilar CCA. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Ishida, Kazuyuki AU - Ishida K AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Osakabe, Mitsumasa AU - Osakabe M AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Eizuka, Makoto AU - Eizuka M AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Tai, Seigo AU - Tai S AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Sugimoto, Ryo AU - Sugimoto R AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Fujita, Yasuko AU - Fujita Y AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Katagiri, Hirokatsu AU - Katagiri H AD - Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Takahara, Takeshi AU - Takahara T AD - Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Uesugi, Noriyuki AU - Uesugi N AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Nitta, Hiroyuki AU - Nitta H AD - Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Sasaki, Akira AU - Sasaki A AD - Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan. FAU - Sugai, Tamotsu AU - Sugai T AD - Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. Electronic address: tsugai@iwate-med.ac.jp. LA - eng PT - Journal Article DEP - 20190808 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (CDX2 Transcription Factor) RN - 0 (CDX2 protein, human) RN - 0 (Keratin-20) RN - 0 (Mucins) RN - EC 3.4.24.11 (Neprilysin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Bile Duct Neoplasms/*metabolism/pathology MH - CDX2 Transcription Factor/*metabolism MH - Cholangiocarcinoma/*metabolism/pathology MH - Female MH - Humans MH - Immunohistochemistry MH - Keratin-20/*metabolism MH - Male MH - Middle Aged MH - Mucins/*metabolism MH - Neprilysin/*metabolism OTO - NOTNLM OT - Distal cholangiocarcinoma OT - Gastrointestinal differentiation marker OT - Immunohistochemistry OT - Patient survival OT - Perihilar cholangiocarcinoma EDAT- 2019/08/12 06:00 MHDA- 2020/06/11 06:00 CRDT- 2019/08/12 06:00 PHST- 2019/04/15 00:00 [received] PHST- 2019/07/28 00:00 [revised] PHST- 2019/08/01 00:00 [accepted] PHST- 2019/08/12 06:00 [pubmed] PHST- 2020/06/11 06:00 [medline] PHST- 2019/08/12 06:00 [entrez] AID - S0046-8177(19)30135-2 [pii] AID - 10.1016/j.humpath.2019.08.002 [doi] PST - ppublish SO - Hum Pathol. 2019 Oct;92:91-100. doi: 10.1016/j.humpath.2019.08.002. Epub 2019 Aug 8.