Assessment of Human Epididymis Protein 4 Expression in Breast Ductal Carcinoma In Situ

Background: /Objectives: Elevated human epididymis protein 4 (HE4) expression has been observed in breast cancer and is linked to cancer progression; however, its role in ductal carcinoma in situ (DCIS) remains unclear. This study evaluated HE4 levels in DCIS serum and tissue and their correlation with clinicopathological features. Methods: Preoperative serum HE4 levels were measured in 59 DCIS patients. HE4 mRNA and protein expression were assessed in DCIS and adjacent normal tissues via RNAscope in situ hybridization and immunohistochemistry. An independent tissue microarray of 41 DCIS cases was also analyzed, and the BreastMark database was applied to explore the prognostic relevance of HE4. Results: Serum HE4 levels (mean ± SD: 39.4 ± 11.9 pmol/L) were within the normal range and did not significantly correlate to clinicopathological parameters except menopause status. HE4 expression was significantly higher in DCIS tissues than in adjacent normal tissues, with mRNA and protein levels positively correlated (r = 0.771, p < 0.001). High HE4 mRNA and protein expression was associated with ER positivity, HER2 negativity, low stromal tumor-infiltrating lymphocyte density, and HR+/HER2- subtypes but did not predict DCIS recurrence. High HE4 expression in breast cancer patients correlated with better survival outcomes. Conclusions: While serum HE4 is not elevated in DCIS, high HE4 expression in tissues is linked to favorable clinicopathological characteristics; thus, further research is warranted on its potential prognostic role.