Department of Gynaecology, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
BJOG. 2023 Jul;130(8):941-948. doi: 10.1111/1471-0528.17417. Epub 2023 Feb 15.
To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH).
Prospective prognostic factor study.
Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England.
Women with AEH or early-stage, low-grade endometrial cancer who were unfit for or declined primary surgical management.
A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed.
Progestin response at 12 months defined by histology and imaging.
The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33-62 years) and 46 kg/m (IQR 38-54 kg/m ), respectively. Baseline serum HE4 was significantly higher in non-responders than responders (119.2 pmol/L, IQR 94.0-208.4 pmol/L versus 71.8 pmol/L, IQR 56.1-84.2 pmol/L, p < 0.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02), baseline serum HE4 (OR 0.97, 95% CI 0.96-0.99, p = 0.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72-0.68, p = 0.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96-0.99, p = 0.008).
Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.
探讨血清人附睾蛋白 4（HE4）作为预测子宫内膜癌和非典型子宫内膜增生（AEH）患者孕激素反应的生物标志物。
前瞻性预后因素研究。
英格兰西北部一家三级妇科肿瘤中心连续采集的女性样本。
不适合或拒绝接受初始手术治疗的 AEH 或早期低级别子宫内膜癌患者。
76 名患有 AEH 或子宫内膜癌的女性接受左炔诺孕酮宫内节育系统（LNG-IUS）治疗 12 个月。进行子宫内膜活检和影像学检查以评估治疗反应。通过化学发光免疫分析法分析治疗前血清 HE4，并进行诊断准确性和逻辑回归分析。
12 个月时的孕激素反应，通过组织学和影像学来定义。
最终队列的中位年龄和体重指数（BMI）分别为 52 岁（四分位间距 [IQR] 33-62 岁）和 46kg/m（IQR 38-54kg/m）。非应答者的基线血清 HE4 明显高于应答者（119.2pmol/L，IQR 94.0-208.4pmol/L 与 71.8pmol/L，IQR 56.1-84.2pmol/L，p<0.001）。年龄较大（比值比 [OR] 0.96，95%置信区间 [CI] 0.93-0.99，p=0.02）、基线血清 HE4（OR 0.97，95%CI 0.96-0.99，p=0.001）和子宫内膜癌组织学（OR 0.22，95%CI 0.72-0.68，p=0.009）与孕激素治疗反应的可能性降低相关。在调整年龄和组织学后，血清 HE4 仍然与孕激素治疗失败独立相关（调整后的危险比 0.97，95%CI 0.96-0.99，p=0.008）。
血清 HE4 有望成为预测子宫内膜癌和 AEH 孕激素治疗反应的生物标志物。
