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.