Comprehensive Immunohistochemical Analysis of Epithelial–Mesenchymal Transition Biomarkers in the Invasive Micropapillary Cancer of the Breast

Abstract

Background: Invasive micropapillary carcinoma (IMPC) of the breast is commonly associated with a poor prognosis due to its high incidence of lymphovascular invasion and lymph node metastasis (LNM). Our study is aimed at investigating the prognostic significance of the expressions of E‐cadherin (E‐cad), N‐cadherin (N‐cad), CD44s, and β‐catenin (β‐cat). In addition, it is aimed at deciphering the consistency of these markers between the IMPC, the invasive breast carcinoma, no‐special type (IBC‐NST), and LNM components in the same IMPC cases.Methods: Sixty‐two IMPC cases with LNM from 1996 to 2018 were analyzed. Immunohistochemical staining was performed separately on the three regions for each patient. Statistical analyses included Kaplan‐Meier, Cox regression, and McNemar’s statistical tests.Results: Loss of CD44 expression in IMPC, IBC‐NST, and LNM areas was associated with poor prognosis in overall survival (OS) (p = 0.010, p < 0.0005, p = 0.025). Loss of CD44 expression in the IBC‐NST, gain of N‐cad expression in the IMPC, and loss of β‐cat expression in the LNM areas were indicators of poor prognosis in disease‐free survival (DFS) (p = 0.005, p = 0.041, p = 0.009).Conclusion: Our evaluation of this rare subtype, focusing on the expression of key epithelial–mesenchymal transition (EMT) molecules, revealed that it shares characteristics with the IBC‐NST component within mixed tumors. Notably, contrary to expectations, a reduction in CD44 expression was found to adversely affect both OS and DFS. By conducting staining procedures simultaneously across three regions within the same patient, a novel approach has provided valuable insights into the mechanisms of EMT.