Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncology (Williston Park). 2013 Jun;27(6):548-56.
HE4 (human epididymis protein 4) is overexpressed in both ovarian and endometrial cancers. Levels of the shed HE4 protein are elevated in sera from ovarian and endometrial cancer patients. HE4 is less frequently elevated than cancer antigen 125 (CA 125) in benign gynecologic conditions and is found in a fraction of endometrial and ovarian cancers that lack CA 125 expression. Consequently, HE4 has emerged as an important biomarker that complements CA 125 in discriminating between benign and malignant pelvic masses, monitoring response to treatment, and detecting recurrences of both ovarian and endometrial cancer. The "risk of ovarian malignancy algorithm" (ROMA) incorporates CA 125, HE4, and menopausal status to distinguish benign from malignant adnexal masses, and has been approved by the US Food and Drug Administration to aid in referring patients who are likely to have ovarian cancer to specially trained gynecologic oncologists for surgery. HE4 also promises to augment the sensitivity of CA 125 for detecting early-stage ovarian cancer. In this review, we discuss the discovery and biologic significance of HE4 and evaluate available evidence regarding the utility of HE4 as a biomarker for ovarian and endometrial cancer.
人附睾蛋白 4(HE4)在卵巢癌和子宫内膜癌中均过度表达。卵巢癌和子宫内膜癌患者血清中脱落的 HE4 蛋白水平升高。在良性妇科疾病中,HE4 的升高频率低于肿瘤标志物 125(CA 125),并且在缺乏 CA 125 表达的一部分子宫内膜癌和卵巢癌中发现。因此,HE4 已成为一种重要的生物标志物,可与 CA 125 联合用于鉴别良性和恶性盆腔肿块,监测治疗反应,并检测卵巢癌和子宫内膜癌的复发。“卵巢恶性肿瘤风险算法”(ROMA)结合了 CA 125、HE4 和绝经状态,以区分良性和恶性附件肿块,并已获得美国食品和药物管理局的批准,以帮助将可能患有卵巢癌的患者转介给专门的妇科肿瘤医生进行手术。HE4 还有望提高 CA 125 检测早期卵巢癌的敏感性。在这篇综述中,我们讨论了 HE4 的发现和生物学意义,并评估了关于 HE4 作为卵巢癌和子宫内膜癌生物标志物的可用证据。