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

## TL;DR

This study examines the role of HE4 in breast ductal carcinoma in situ and finds that high tissue HE4 expression is linked to favorable features but not elevated in blood.

## Contribution

The study reveals that HE4 tissue expression in DCIS correlates with specific clinicopathological features and may have prognostic value.

## Key findings

- HE4 expression in DCIS tissues is significantly higher than in adjacent normal tissues.
- High HE4 expression correlates with ER positivity, HER2 negativity, and HR+/HER2− subtypes.
- High HE4 expression in breast cancer patients is associated with improved survival outcomes.

## Abstract

Background/Objectives: Elevated expression of human epididymis protein 4 (HE4) has been observed in breast cancer and is associated with cancer progression; however, its role in ductal carcinoma in situ (DCIS) remains unclear. This study aimed to evaluate HE4 levels in serum and tissue from patients with DCIS and their correlation with clinicopathological features. Methods: Preoperative serum HE4 levels were measured in 59 DCIS patients. HE4 mRNA and protein expression in DCIS and adjacent normal tissues were assessed using RNAscope in situ hybridization and immunohistochemistry, respectively. An additional independent tissue microarray of 41 DCIS cases was also analyzed for HE4 expression in tumor tissue only. Furthermore, the BreastMark database was applied to assess the prognostic significance of HE4 expression in a larger cohort of breast cancer. Results: Serum HE4 levels (mean ± SD: 39.4 ± 11.9 pmol/L) were within the normal range and showed no significant correlation with clinicopathological parameters except menopausal status. HE4 expression was significantly higher in DCIS tissues compared to adjacent normal tissues, with a positive correlation between mRNA and protein levels (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 was not predictive of DCIS recurrence. In breast cancer patients, high HE4 expression was significantly correlated with improved survival outcomes. Conclusions: Although serum HE4 is not elevated in DCIS, high HE4 expression in tissue is associated with favorable clinicopathological features. These findings highlight the need for further investigation into the potential prognostic role of HE4.