Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 16, 2017; 5(1): 1-8
Published online Jan 16, 2017. doi: 10.12998/wjcc.v5.i1.1
Inverse correlation between CD8+ inflammatory cells and E-cadherin expression in gallbladder cancer: Tissue microarray and imaging analysis
Keita Kai, Masanori Masuda, Shinichi Aishima
Keita Kai, Shinichi Aishima, Department of Pathology, Saga University Hospital, Saga 849-8501, Japan
Masanori Masuda, Shinichi Aishima, Department of Pathology and Microbiology, Saga University Faculty of Medicine, Saga 849-8501, Japan
Author contributions: Kai K is the main author of this article and performed the data correction and statistical analyzes; Masuda M contributed to the data collection; Aishima S reviewed the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: The study protocol was approved by the Ethics Committee of the Faculty of Medicine at Saga University (approval no. 27-19).
Informed consent statement: Written informed consent for the use of resected tissue and clinical information was obtained from all patients.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Keita Kai, Department of Pathology, Saga University Hospital, Nabeshima 5-1-1, Saga 849-8501, Japan.
Telephone: +81-952-343264 Fax: +81-952-342055
Received: June 22, 2016
Peer-review started: June 27, 2016
First decision: August 11, 2016
Revised: August 27, 2016
Accepted: October 25, 2016
Article in press: October 27, 2016
Published online: January 16, 2017

To investigated the association between the tumor cells’ expression of E-cadherin and the numbers of several types of inflammatory cells infiltrating into the invasive portion of gallbladder cancer (GBC).


We analyzed 50 GBC cases for which a sufficient amount of tumor tissues for tissue microarray (TMA) had been saved. Three tissue cores (3.0 mm) of invasive lesion from each case were used for the TMA. The 4-μm cut sections on slides were immunostained using primary antibodies including E-cadherin for cancer cells, leukocyte common antigen for leukocyte, myeloperoxidase for neutrophils, CD3 for T cells, CD4 for helper T cells, CD8 for killer T cells, CD20 for B cells and CD68 for macrophages. The immunostained slides were digitally analyzed by imaging analysis software.


A significant inverse correlation between the number of infiltrating CD8+ cells at invasive areas and the expression of E-cadherin by cancer cells was observed (P = 0.0001), although the degree of this correlation was relatively weak (R = 0.32). The number of CD8+ cells and the cancer cells’ E-cadherin expression were also significantly correlated with tumor differentiation (well-differentiated vs poorly differentiated) (P = 0.0467 and P = 0.0294, respectively). Inverse correlation of T-stage and the number of CD8+ cell infiltration was observed with statistical significance in comparison of T2 and T3 cases (P = 0.0324).


Our findings indicate an inverse correlation of CD8+ T cell infiltration and cancer cells’ E-cadherin expression at invasive areas of GBC. Further analyses are essential to test these findings.

Keywords: E-cadherin, Inflammation, CD8, Gallbladder cancer, Tissue microarray

Core tip: We analyzed the association between the expression of E-cadherin in tumor cells and the type and amount of inflammatory cells infiltrating into the invasive portion of gallbladder cancer, using tissue microarray and imaging analyses. The results indicated an inverse correlation of CD8+ T cell infiltration and E-cadherin expression by cancer cells at invasive areas of gallbladder cancer. Further analyses are essential to test these results.