HE4 (эпителиальный рак яичников)

Human epididymis protein 4 (HE4, also known as WFDC2) is used to assess risk and guide management of epithelial ovarian cancer and endometrial carcinoma. The HE4 test supports diagnostic evaluation of adnexal masses, complements CA-125—particularly in CA-125–negative disease—and is incorporated with menopausal status into the ROMA algorithm for malignancy risk estimation. It also assists with prognostic stratification, as higher concentrations correlate with advanced FIGO stage and aggressive tumor biology, and it is used to monitor response to therapy and to surveil for recurrence.

HE4 is a small secreted protein of approximately 25 kDa in the whey acidic protein four-disulfide core family. It was first identified in the distal epithelium of the epididymal duct, but it is also produced by multiple tissues, including glandular epithelium of the breast and the female and male reproductive tracts, distal renal tubules, colon, and salivary glands. Its physiologic functions are not fully defined; current data suggest roles in maintaining epithelial homeostasis and supporting innate immune defenses in the respiratory tract and oral cavity. Pathologic overexpression of HE4 is documented in several malignancies, including mesothelioma and cancers of the lung, kidney, breast, endometrium, and gastrointestinal tract, and experimental data indicate that HE4 can promote tumor progression by enhancing ovarian cancer cell migration and adhesion. Clinically, the marker is most valuable in ovarian and endometrial cancers for diagnosis, prognostic assessment, and treatment monitoring. In the differential diagnosis of pelvic masses, HE4 shows higher specificity than CA-125 because it is less frequently elevated in benign conditions (8% vs 29%); CA-125 rises in 67% of endometriosis cases, whereas HE4 increases in only 3%. Combining HE4 with CA-125 and menopausal status improves risk discrimination and underpins the ROMA algorithm. No single blood test reliably screens for early ovarian cancer. CA-125 lacks adequate sensitivity at early stages (30%–50%), while HE4 can be detected in 32% of ovarian cancers that are CA-125–negative, providing complementary information. HE4 is included in several proposed multimarker screening panels; a panel comprising HE4, CA-125, carcinoembryonic antigen (CEA), and vascular cell adhesion molecule-1 (VCAM-1) has reported sensitivity of 86% and specificity of 98% for early-stage ovarian cancer. Both HE4 and CA-125 primarily reflect epithelial ovarian tumors and do not detect germ cell or sex cord–stromal neoplasms. Some studies also suggest utility of HE4 in endometrial cancer screening. Higher HE4 concentrations associate with greater FIGO stage, higher grade, and more aggressive phenotypes in ovarian and endometrial carcinomas, indicating worse prognosis. For therapy assessment, HE4 levels differ markedly at diagnosis compared with complete clinical remission (324.1 vs 23.3 pmol/L). In ovarian cancer surveillance, HE4 may rise approximately 4.5 months before clinical recurrence; using a threshold above 70 pmol/L, HE4 detects recurrence with 74% sensitivity and 100% specificity, and combining HE4 with CA-125 increases sensitivity to 76%. In endometrial cancer, HE4 is elevated in 80% of recurrences and, at concentrations above 70 pmol/L, yields 81% sensitivity and 64% specificity. Interpretation requires clinical context. HE4 may be increased in non-gynecologic conditions such as lung cancer, renal failure, and renal fibrosis. Concentrations rise substantially with age (by contrast, CA-125 typically declines with age); the 95th percentile is 128 pmol/L in postmenopausal women and 89 pmol/L in premenopausal women. Pregnant women have substantially lower HE4 levels than nonpregnant women. Menstrual cycle phase, endometriosis, and use of estrogen- or progesterone-containing contraceptives do not affect HE4 concentrations. Results should be considered alongside relevant history, examination findings, and other laboratory data.