Kim Nah Ihm, Park Min Ho, Lee Ji Shin
Department of Pathology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Department of Surgery, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Diagnostics (Basel). 2025 Apr 22;15(9):1058. doi: 10.3390/diagnostics15091058.
: 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. : 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. : 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 ( = 0.771, < 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. : 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.
: 已观察到人类附睾蛋白4（HE4）在乳腺癌中表达升高，并与癌症进展相关；然而，其在导管原位癌（DCIS）中的作用仍不清楚。本研究旨在评估DCIS患者血清和组织中的HE4水平及其与临床病理特征的相关性。: 测量了59例DCIS患者术前血清HE4水平。分别使用RNAscope原位杂交和免疫组织化学评估DCIS及相邻正常组织中HE4 mRNA和蛋白表达。还对41例DCIS病例的另一个独立组织芯片仅分析肿瘤组织中的HE4表达。此外，应用BreastMark数据库评估HE4表达在更大队列乳腺癌中的预后意义。: 血清HE4水平（均值±标准差：39.4±11.9 pmol/L）在正常范围内，除绝经状态外，与临床病理参数无显著相关性。DCIS组织中HE4表达明显高于相邻正常组织，mRNA和蛋白水平呈正相关（=0.771，<0.001）。HE4 mRNA和蛋白高表达与雌激素受体（ER）阳性、人表皮生长因子受体2（HER2）阴性、低基质肿瘤浸润淋巴细胞密度及HR+/HER2-亚型相关，但不能预测DCIS复发。在乳腺癌患者中，HE4高表达与生存结局改善显著相关。: 虽然DCIS患者血清HE4未升高，但组织中HE4高表达与良好的临床病理特征相关。这些发现凸显了进一步研究HE4潜在预后作用的必要性。
