TY - JOUR
T1 - Expression of Epithelial-Mesenchymal Transition Proteins in Pancreatic Anaplastic (Undifferentiated) Carcinoma
AU - Ishida, Kazuyuki
AU - Yamashita, Rina
AU - Osakabe, Mitsumasa
AU - Uesugi, Noriyuki
AU - Yamada, Noriyuki
AU - Nitta, Hiroyuki
AU - Fujishima, Fumiyoshi
AU - Motoi, Fuyuhiko
AU - Suzuki, Hiroyoshi
AU - Shimamura, Hiromune
AU - Noda, Yutaka
AU - Sawai, Takashi
AU - Unno, Michiaki
AU - Sasano, Hironobu
AU - Sasaki, Akira
AU - Sugai, Tamotsu
N1 - Funding Information:
From the Departments of *Molecular Diagnostic Pathology and †Surgery, Iwate Medical University, Morioka; and Departments of ‡Pathology and §Surgery, Tohoku University Graduate School of Medicine; Departments of ||Pathology and Laboratory Medicine and ¶Surgery, National Hospital Organization Sendai Medical Center; and #Department of Pathology, Sendai City Medical Center, Sendai, Japan. Received for publication January 13, 2018; accepted October 16, 2018. Address correspondence to: Tamotsu Sugai, MD, PhD, Department of Molecular Diagnostic Pathology, Iwate Medical University, 19–1, Uchimaru, Morioka, Iwate 020-8505, Japan (e‐mail: tsugai@iwate-med.ac.jp). This work was supported by JSPS KAKENHI grant JP16K08655. The authors declare no conflict of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.pancreasjournal.com). Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. DOI: 10.1097/MPA.0000000000001199
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Objectives The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT). Methods Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box-binding homeobox 1). Expression score was determined based on staining intensity and stained area of the target cells. Finally, we performed a hierarchical clustering based on the expression pattern of E-cadherin and EMT-related proteins of the sarcomatous component. Results The expression score of E-cadherin decreased in the order of sarcomatous > transitional > carcinomatous components (P < 0.01). Although there were significant differences in the immunohistochemical scores of Slug, Twist, and Zeb1 between carcinomatous and transitional components (P < 0.01), the significant difference in immunohistochemical score of Zeb1 between transitional and sarcomatous components was found (P < 0.05). Furthermore, APCs were divided into 2 subgroups based on the expression patterns of E-cadherin and EMT-related proteins (hierarchical clustering analysis). Consequently, these subgroups were distinguished by Twist expression. Conclusions Epithelial-mesenchymal transition plays an essential role in the pathogenesis of APC.
AB - Objectives The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT). Methods Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box-binding homeobox 1). Expression score was determined based on staining intensity and stained area of the target cells. Finally, we performed a hierarchical clustering based on the expression pattern of E-cadherin and EMT-related proteins of the sarcomatous component. Results The expression score of E-cadherin decreased in the order of sarcomatous > transitional > carcinomatous components (P < 0.01). Although there were significant differences in the immunohistochemical scores of Slug, Twist, and Zeb1 between carcinomatous and transitional components (P < 0.01), the significant difference in immunohistochemical score of Zeb1 between transitional and sarcomatous components was found (P < 0.05). Furthermore, APCs were divided into 2 subgroups based on the expression patterns of E-cadherin and EMT-related proteins (hierarchical clustering analysis). Consequently, these subgroups were distinguished by Twist expression. Conclusions Epithelial-mesenchymal transition plays an essential role in the pathogenesis of APC.
KW - carcinosarcoma
KW - epithelial-mesenchymal transition
KW - pancreas
KW - pancreatic ductal adenocarcinoma
KW - undifferentiated (anaplastic) carcinoma
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U2 - 10.1097/MPA.0000000000001199
DO - 10.1097/MPA.0000000000001199
M3 - Article
C2 - 30451796
AN - SCOPUS:85058602970
VL - 48
SP - 36
EP - 42
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 1
ER -