Retained cell–cell adhesion in serrated neoplastic pathway as opposed to conventional colorectal adenomas

Abstract

The molecular features of serrated polyps of colorectum remain to be elucidated. The expression pattern of adhesive molecules (E-cadherin, α-catenin, and β-catenin) has not been examined in serrated neoplastic pathway. The expression of E-cadherin, α-catenin, and β-catenin were analyzed by immunohistochemistry in 32 hyperplastic polyps (HPs), 28 sessile serrated adenomas (SSAs), 37 traditional serrated adenomas (TSAs), 51 traditional adenomas (TAs), and 10 normal colonic tissues (NCs). Retained membranous expression for E-cadherin, α-catenin, and β-catenin was more frequent in HPs, SSAs, and TSAs than that in TAs (p < 0.001). Nuclear labeling of β-catenin was detected in 19.6% of TAs, but in none of HPs, SSAs, and TSAs (p < 0.001). Cytoplasmic accumulation of β-catenin was found in 3.1% of HPs, 3.6% of SSAs, and 21.6% of TSAs, significantly lower than that in TAs (60.8%, p < 0.001). The membranous co-expression of E-cadherin, α-catenin, and β-catenin was more frequent in HPs (68.8%), SSAs (60.7%), and TSAs (37.8%) than that in TAs (7.8%, p < 0.001). Cell adhesion function is retained in serrated neoplastic pathway. Wnt signaling pathway plays a less active role in the development of colorectal serrated polys than in TAs.

Figure 1.

Histological appearance of a typical sessile serrated adenoma (SSA) and a traditional serrated adenoma (TSA) showing serrated architecture, hematoxylin and eosin (H&E) staining. Scale bars = 100 µm, 100 × magnification.

Figure 2.

Representative immunohistochemical staining patterns for E-cadherin, α-catenin, and β-catenin in a TA showing: normal membranous expression of E-cadherin, α-catenin and β-catenin in the normal adjacent tissue (white arrows), and absence of E-cadherin and α-catenin expression in adenomatous epithelium (black arrows). Abnormal nuclear expression of β-catenin was seen in adenomatous epithelium (black arrow). Scale bars = 100 µm, 200 × magnification.

Figure 3.

Expression of E-cadherin, α-catenin, and β-catenin in a hyperplastic polyp (HP). Expression of all three components was confined to the cell borders of epithelial cells, with no expression in the surrounding mesenchymal cells. Scale bars = 100 µm, 200 × magnification.

Figure 4.

In a sessile serrated adenoma (SSA), E-cadherin, α-catenin, and β-catenin were expressed in the cell membrane. Scale bars = 100 µm, 200 × magnification.

Figure 5.

Traditional serrated adenoma (TSA) (lower part, T) with foci of sessile serrated adenoma (SSA) (upper part, S). Retained membranous distribution of E-cadherin, α-catenin, and β-catenin staining was seen in both the SSA part and TSA part. MP, mixed polyp. Scale bars = 100 µm, 200 × magnification.

Figure 6.

Positive membranous immunohistochemical staining of E-cadherin, α-catenin, and β-catenin in a pure traditional serrated adenoma (TSA). Scale bars = 100 µm, 200 × magnification.