Clinicopathological observation and initial exploration of characteristic biomarkers in breast apocrine carcinoma

OBJECTIVE: This study seeks to characterize the clinicopathological features of a cohort of breast apocrine carcinomas (AC) in the Chinese population, investigate their biological properties through immunohistochemistry and proteomics, and conduct a preliminary exploration of their biologically relevant molecules. METHODS: Specimens from 12 female patients (median age 52 years) with AC of the breast were obtained from the Department of Pathology of Shandong University of Traditional Chinese Medicine Affiliated Hospital from 2019 to 2024. Clinical pathological features were observed, and relevant immunohistochemical staining and KEGG pathway enrichment analysis were performed. Additionally, three cases each of triple-negative apocrine carcinoma (TNAC) and luminal androgen receptor triple-negative breast cancer (LAR-TNBC) were included for comparative analysis. Proteomic profiling and assessment of TRPS1 gene amplification were performed to elucidate the differences between these entities. RESULTS: In 75% of patients (9/12), the tumours were located in the upper outer quadrant; 50% (6/12) exhibited invasive apocrine carcinoma (IAC) with apocrine-type ductal carcinoma in situ (ADCIS). All cases exhibited an apocrine morphology and were AR/GCDFP-15 positive and ER/PR-negative. CD10 was expressed in a patchy pattern in the marginal zone of the breast in IAC and was highly expressed in ADCIS but not expressed in apocrine metaplasia. The linear development pattern of breast AC (6 cases) was significantly associated with Her-2 positivity (66.7% vs. 33.3%). Hypoxia-inducible factor-1α(HIF-1α) expression was significantly higher in IAC than in ADCIS (p < 0.01) and was associated with invasion. IL-10 was continuously highly expressed in the tumour microenvironment. KEGG analysis revealed AR-Cyclin D1 pathway enrichment; the proteomic analysis revealed significant differences between the TNAC and LAR-TNBC groups (more than 200 differentially expressed proteins (DEPs)).TRPS1 amplification was significantly greater in the LAR-TNBC group (100%, 3/3) than in the AC group. The median follow-up was 6–39 months, with no recurrence or metastasis (100% disease-free survival). CONCLUSIONS: AC exhibits unique AR-driven characteristics and an apocrine morphological lineage. CD10, Cyclin D1, and HIF-1α are potential biologically relevant markers. TNAC significantly differs from LAR-TNBC in terms of its proteomic and TRPS1 amplification characteristics, supporting its classification as an independent disease type.