PS2-05-21: Altered expression of catenins and cadherins in lobular breast cancer: A focus on beta-catenin and E-cadherin

Abstract Background: Dysfunction of the E-cadherin/catenin complex is a hallmark of invasive lobular carcinoma (ILC) of the breast, which is associated with poorer long-term outcomes compared to invasive ductal carcinoma (IDC). However, accurate histologic diagnosis of ILC remains challenging due to complex morphologic and immunohistochemical (IHC) patterns. This study aimed to compare the expression patterns of E-cadherin, beta-catenin, and P120 catenin in breast carcinomas, focusing on aberrant patterns and their clinicopathologic significance. Methods: We retrospectively analyzed 264 breast carcinoma cases with suspected lobular morphology. Tissue microarray (TMA) blocks were constructed from surgical specimens. IHC for E-cadherin, beta-catenin, P120 catenin, N-cadherin, and P-cadherin was performed on TMA sections, and staining patterns were classified as membranous, aberrant, or loss. Results: Morphologically, 43 cases (16.3%) showed IDC features and 221 (83.7%) showed ILC features. After integrating IHC results, 18 cases (6.8%) were classified as IDC and 246 (93.2%) as ILC based on aberrant or loss of marker expression. The distribution of staining patterns was similar among E-cadherin, beta-catenin, and P120 catenin, with a high concordance (95.1%) between E-cadherin and beta-catenin. Beta-catenin demonstrated a distinct Golgi pattern in aberrant cases, enhancing interpretability and sensitivity compared to E-cadherin and P120 catenin. Interpretation of P120 staining was sometimes difficult due to the small size of lobular carcinoma cells and the presence of intracytoplasmic vacuoles. Twelve cases (4.5%) showed discordant results between E-cadherin and beta-catenin, with beta-catenin being more sensitive in detecting aberrant/loss patterns. Aberrant beta-catenin expression was significantly associated with higher N and M stage, higher histologic grade, lymphovascular invasion, lower estrogen receptor (ER) expression, higher HER2 expression, and increased N-cadherin and P-cadherin expression. Conclusions: Beta-catenin IHC is more sensitive and interpretable than E-cadherin or P120 catenin for distinguishing ILC from IDC, due to its unique localization patterns. Aberrant expression of adhesion complex molecules, especially beta-catenin, is associated with adverse clinicopathologic features and may reflect atypical features among breast carcinomas. These findings support incorporating beta-catenin IHC into the diagnostic workup of breast carcinomas with ambiguous morphology. Citation Format: T. Jeon, Y. Sung, J. Lee, J. Oh, J. Ahn, A. Kim. Altered expression of catenins and cadherins in lobular breast cancer: A focus on beta-catenin and E-cadherin [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-21.