Association of tumor budding with Nectin-4 and E-cadherin expression in breast carcinomas

Breast cancer is the most common cancer among women and one of the leading causes of cancer-related deaths. In the literature, tumour budding has been associated with a poor prognosis, particularly in colorectal adenocarcinomas. Similarly, tumour budding is considered a prognostic marker in breast carcinomas. Our study aimed to compare tumour budding with clinical and pathological parameters, and to investigate its relationship with E-cadherin and Nectin-4 expression. The study included 182 cases of invasive breast carcinoma diagnosed between 2015 and 2024 at the Department of Pathology, Faculty of Medicine, Dicle University. We examined the relationships between tumour budding and clinical-pathological data such as age, tumour size, histological type, histological grade, lymphovascular invasion, perineural invasion, lymph node involvement, accompanying ductal carcinoma in situ, hormone receptor status, tumour stage and immunohistochemical subtype. Additionally, Nectin-4 and E-cadherin expression was evaluated immunohistochemically and their correlation with tumour budding was analysed statistically. The analysis revealed that high tumour budding was significantly associated with an advanced histological grade, high Nectin-4 expression and histological type. Furthermore, cases with high tumour budding exhibited a higher incidence of lymph node metastasis and a more advanced N stage. When cases were grouped according to subtypes defined by biomarkers, a significant association was found between high tumour budding and lymph node metastasis, lymphovascular invasion and N stage in the luminal A group. In the luminal B group, high Nectin-4 expression was significantly associated with high tumour budding. Comparing Nectin-4 with clinical-pathological parameters revealed a significant association between high Nectin-4 expression and ER negativity. Tumour budding is an important histopathological finding reflecting increased invasiveness in breast carcinomas and shows significant associations with certain clinical-pathological parameters and expression levels of cellular adhesion molecules. High Nectin-4 expression can be considered a molecular change that may play a role in tumor progression. These findings suggest that tumor budding may be both a prognostic parameter and associated with potential molecular targets. Keywords: Breast carcinoma, tumor budding, Nectin-4, E-cadherin