Reduction in membranous immunohistochemical staining for the intracellular domain of epithelial cell adhesion molecule correlates with poor patient outcome in primary colorectal adenocarcinoma

  • A. Wang Kingston General Hospital; Queen’s University
  • R. Ramjeesingh Kingston General Hospital; Queen’s University
  • C.H. Chen Kingston General Hospital; Queen’s University
  • D. Hurlbut Kingston General Hospital; Queen’s University
  • N. Hammad Kingston General Hospital; Queen’s University
  • L.M. Mulligan Kingston General Hospital; Queen’s University
  • C. Nicol Kingston General Hospital; Queen’s University
  • H.E. Feilotter Kingston General Hospital; Queen’s University
  • S. Davey Kingston General Hospital; Queen’s University
Keywords: Colon cancer, EpCAM, biomarkers

Abstract

Background

Epithelial cell adhesion molecule (EpCAM) is a multifunctional transmembrane glycoprotein expressed on both normal epithelium and epithelial neoplasms such as gastric, breast, and renal carcinomas. Recent studies have proposed that the proteolytic cleavage of the intracellular domain of EpCAM (EpCAM-ICD) can trigger signalling cascades leading to aggressive tumour behavior. The expression profile of EpCAM-ICD has not been elucidated for primary colorectal carcinoma. In the present study, we examined EpCAM-ICD immunohistochemical staining in a large cohort of patients with primary colorectal adenocarcinoma and assessed its performance as a potential prognostic marker.

Methods

Immunohistochemical staining for EpCAM-ICD was assessed on tissue microarrays consisting of 137 primary colorectal adenocarcinoma samples. Intensity of staining for each core was scored by 3 independent pathologists. The membranous EpCAM-ICD staining score was calculated as a weighted average from 3 core samples per tumour. Univariate analysis of the average scores and clinical outcome measures was performed.

Results

The level of membranous EpCAM-ICD staining was positively associated with well-differentiated tumours (p = 0.01); low preoperative carcinoembryonic antigen (p = 0.001); and several measures of survival, including 2-year (p = 0.02) and 5-year survival (p = 0.05), and length of time post-diagnosis (p = 0.03). A number of other variables — including stage, grade, and lymph node status—showed correlations with EpCAM staining and markers of poor outcome, but did not reach statistical significance.

Conclusions

Low membranous EpCAM-ICD staining might be a useful marker to identify tumours with aggressive clinical behavior and potential poor prognosis and might help to select candidates who could potentially benefit from treatment targeting EpCAM.


Author Biographies

A. Wang, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
R. Ramjeesingh, Kingston General Hospital; Queen’s University
Department of Oncology
C.H. Chen, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
D. Hurlbut, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
N. Hammad, Kingston General Hospital; Queen’s University
Department of Oncology
L.M. Mulligan, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
C. Nicol, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
H.E. Feilotter, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
S. Davey, Kingston General Hospital; Queen’s University
Departments of Pathology and Molecular Medicine and of Biomedical and Molecular Sciences
Published
2016-06-13
How to Cite
Wang, A., Ramjeesingh, R., Chen, C., Hurlbut, D., Hammad, N., Mulligan, L., Nicol, C., Feilotter, H., & Davey, S. (2016). Reduction in membranous immunohistochemical staining for the intracellular domain of epithelial cell adhesion molecule correlates with poor patient outcome in primary colorectal adenocarcinoma. Current Oncology, 23(3), e171-e178. https://doi.org/10.3747/co.23.3028
Section
Biomarkers in Oncology