Association Between the Immunohistochemistry Expression of E-cadherin, Beta-Catenin, and CD44 in Colorectal Adenocarcinoma

Abstract

Background Colorectal cancer is a leading cause of cancer-related deaths worldwide, and epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. In EMT, there is downregulation of E-cadherin, an intracellular adhesion molecule, as well as mutations in beta-catenin genes. On immunohistochemistry (IHC), the expression of CD44 portrays stem cell differentiation, which, in turn, is strongly associated with EMT. Thus, newer targeted therapies can be advised based on the expression of EMT and stem cell differentiation. Aims and objectives To determine the IHC expression of E-cadherin, beta-catenin, and CD44 in colorectal adenocarcinoma and find the association of the IHC expression of E-cadherin, beta-catenin, and CD44 with the histopathological grade, stage, lymph node metastasis, and lymphovascular invasion of colorectal adenocarcinoma. Materials and methods Fifty histologically proven cases of colorectal adenocarcinoma from 2016 to 2021 were included in this study, and clinicopathological data including age, gender, grading, TNM (tumour, node, and metastasis) staging, and lymph node metastasis were collected and hematoxylin and eosin slides were reviewed. IHC staining for E-cadherin, beta-catenin, and CD44 was done for all cases using the peroxidase and anti-peroxidase method, and the results were analysed. Results Peak incidence occurred in the 61-70 years age group (36%), and the most common site of the tumour was the rectal area (48%). The majority of the cases were in TNM stage II (37.3%), and a low expression of E-cadherin was found to be associated with higher T stage (p = 0.03), TNM staging (p = 0.04), as well as the presence of lymph node metastasis (p = 0.006). High beta-catenin expression was observed to have a significant correlation with a higher T stage (p = 0.006) and TNM staging (p = 0.005), while high CD44 expression was found to be associated with lymph node metastasis (p = 0.01). Altered expression of EMT-related proteins (E-cadherin and beta-catenin) showed a significant correlation with higher T stage (p = 0.03), TNM staging (p = 0.016), and lymph node metastasis (0.04). Conclusions EMT and cancer stem cell IHC markers are biomarkers for aggressive tumour growth and lymph node metastasis. Hence, EMT markers (E-cadherin and beta-catenin) and cancer stem cell markers (CD44) can be used as prognostic markers.

Wnt signaling-associated proteins, β-catenin, and E-cadherin as a potential immunohistochemical bi-omarker of the progression of adenoma to colorectal carcinoma

“…Increased expression of β-catenin showed a strong association with increasing grading and staging of the tumor with lymph node metastases, which was also seen in the studies by Choi et al 21 and Tunuguntla et al 25 and decreased expression in adenomas. However, no such association was found in other studies by Gomaa et al 23 Our result showed the gradual intracellular translocation of β-catenin from a membranous to a nuclear expression in a stepwise manner, following the polyp-adenoma-carcinoma sequence, which is in concordance with the findings of Wong et al 28 In this study a statistically significant changes in the subcellular localization and increase in β-catenin expression was noted between benign and malignant neoplasms, with the subsequent presence of a higher nuclear β-catenin score in the malignant neoplasms.…”

“…Consistent with the studies by Iseki et al 22 , Gomaa et al 23 , and Melincovici et al 24 had a male predominance. Conversely, the studies by Choi et al 21 and Tunuguntla et al 25 show female preponderance. In the present study, 52.9% of malignant cases were considered T3 stage, and similar findings were observed by Gomaa et al 23 , Melincovici et al 24 and Tunuguntla et al 25 , whereas the T4 stage was the major type in the study by Iseki et al 22 .…”

“…and Melincovici et al 24 found a significant association between the loss of expression of E-cadherin and cancer grading. Tunuguntla et al 25 shows significant correlation with tumor staging and lymph node metastases. Similarly, in another study, loss of E-cadherin being indispensable in transformation from adenoma to carcinoma sequence in CRC 26 .…”

E-Cadherin Expression Varies Depending on the Location within the Primary Tumor and Is Higher in Colorectal Cancer with Lymphoid Follicles

“…Conventional prognostic parameters for CRC include tumor staging and grading, metastases, and, additionally, lymphatic, perineural, and venous invasion. However, one study also assessed E-cadherin expression depending on these markers, and it turned out that most CRC patients had tumors with low (60%) E-cadherin expression, which was significantly associated with a higher T stage, the presence of lymph node metastasis, and TNM staging [ 4 ]. In another recent study, the immunohistochemical staining, protein expression, and mRNA level of E-cadherin were lower in tumors than in normal tissues, and the expression levels of E-cadherin were significantly associated with the pathological classification, lymph node, distal metastasis, and TNM stage [ 5 ].…”