ALK protein expression and gene copy number alterations in triple-negative breast cancer: Clinical implications

Anaplastic lymphoma kinase (ALK) is a well-established oncogenic driver in non-small cell lung cancer (NSCLC), but its role in triple-negative breast cancer (TNBC) remains largely unexplored. In this study, we examined the expression and gene status of ALK in 208 TNBC cases using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). ALK protein positivity was identified in 19.2% of cases, significantly correlating with histological subtype, p53 mutation status, and Ki67 index. Among the 156 basal-like breast carcinoma (BLBC) cases, ALK presented three distinct localization patterns: diffuse cytoplasmic granular, cytoplasmic/membranous, and cytoplasmic/nuclear. ALK gene copy number abnormalities were detected in 16.8% of cases, with a higher prevalence in p53-mutant and high Ki67 expression tumors. Notably, ALK protein positivity and gene copy number gain were associated with poorer survival outcomes, including 5-year overall survival (OS) and 10-year recurrence-free survival (RFS). Our findings highlight the importance of ALK as a potential therapeutic target in TNBC, emphasizing the need for further investigation into its clinical significance.