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结直肠癌中E-钙黏蛋白、β-连环蛋白和CD44的免疫组织化学表达之间的关联

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

作者信息

Tunuguntla Amrutha, Suresh T N, Pn Sreeramulu

机构信息

Department of Pathology, Sri Devaraj Urs Medical College, Kolar, IND.

Department of Surgery, R.L. Jalappa Hospital and Research Centre, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, IND.

出版信息

Cureus. 2023 Mar 2;15(3):e35686. doi: 10.7759/cureus.35686. eCollection 2023 Mar.

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.

摘要

背景

结直肠癌是全球癌症相关死亡的主要原因之一,上皮-间质转化(EMT)在癌症转移中起重要作用。在EMT过程中,细胞内粘附分子E-钙粘蛋白表达下调,同时β-连环蛋白基因发生突变。在免疫组织化学(IHC)中,CD44的表达描绘了干细胞分化,而这又与EMT密切相关。因此,可根据EMT和干细胞分化的表达情况建议采用更新的靶向治疗方法。

目的

确定E-钙粘蛋白、β-连环蛋白和CD44在结直肠腺癌中的IHC表达,并找出E-钙粘蛋白、β-连环蛋白和CD44的IHC表达与结直肠腺癌的组织病理学分级、分期、淋巴结转移及淋巴管侵犯之间的关联。

材料与方法

本研究纳入了2016年至2021年50例经组织学证实的结直肠腺癌病例,收集了包括年龄、性别、分级、TNM(肿瘤、淋巴结和转移)分期及淋巴结转移等临床病理数据,并对苏木精和伊红染色切片进行了复查。对所有病例采用过氧化物酶和抗过氧化物酶法进行E-钙粘蛋白、β-连环蛋白和CD44的IHC染色,并对结果进行分析。

结果

发病高峰出现在61-70岁年龄组(36%),肿瘤最常见的部位是直肠区域(48%)。大多数病例处于TNM II期(37.3%),发现E-钙粘蛋白低表达与更高的T分期(p = 0.03)、TNM分期(p = 0.04)以及淋巴结转移的存在(p = 0.006)相关。观察到β-连环蛋白高表达与更高的T分期(p = 0.006)和TNM分期(p = 0.005)显著相关,而CD44高表达与淋巴结转移相关(p = 0.01)。EMT相关蛋白(E-钙粘蛋白和β-连环蛋白)的表达改变与更高的T分期(p = 0.03)、TNM分期(p = 0.016)和淋巴结转移(0.04)显著相关。

结论

EMT和癌症干细胞IHC标志物是侵袭性肿瘤生长和淋巴结转移的生物标志物。因此,EMT标志物(E-钙粘蛋白和β-连环蛋白)和癌症干细胞标志物(CD44)可用作预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e56e/10066707/d4193e695735/cureus-0015-00000035686-i01.jpg

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