HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status

HE4 as a Biomarker for Endometrial Cancer

“…There is growing evidence that HE4 may be useful as a prognostic marker in EC, with many studies showing an association between serum HE4 and poor prognostic histopathological factors, including ≥50% MI [ 27 , 31 , 35 , 42 , 55 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ], CI and stage [ 42 , 60 , 65 , 66 , 69 ], presence of LVSI [ 31 , 42 , 55 , 60 , 64 , 66 , 68 , 69 ], tumour size [ 31 , 55 , 67 , 68 , 69 , 70 ] and LNM [ 27 , 31 , 32 , 44 , 55 , 60 , 64 , 65 , 68 , 69 ]. Capriglione et al demonstrated that the proportion of EC patients with a cut-off of HE4 >70 pM was 42%, 77%, 90%, 93% and 100% at stages IA, IB, II, III and IV, respectively, and suggested ideal serum HE4 cut-offs by stage with >80% sensitivity and >95% specificity [ 71 ].…”

“…Other studies have similarly shown serum HE4 is an independent predictive biomarker of OS when adjusted for age, FIGO stage, grade, MI, LNM and LVSI [ 64 , 66 ]. Another study of patients with EC receiving a median follow up of 48 months post-surgery showed that the median HE4 in the nine (6%) patients that died was significantly higher at 109 pM compared to 77 pM in survivors [ 68 ]. Insin et al showed that three-year OS was poorer (71% vs. 96%) in patients with pre-operative serum HE4 ≥ 70 pM who had surgery [ 80 ].…”

“…A limited number of studies have looked at the sensitivity of HE4 and CA125 in combination for detecting poor prognostic features such as LNM, with mixed results [ 67 , 68 , 73 ]. Wang et al reported a higher sensitivity of HE4 and CA125 than HE4 alone for detection of LNM (94% vs. 82%), but the specificity was significantly lower (30% vs. 52%) [ 67 ].…”

“…Wang et al reported a higher sensitivity of HE4 and CA125 than HE4 alone for detection of LNM (94% vs. 82%), but the specificity was significantly lower (30% vs. 52%) [ 67 ]. In contrast, O’Toole et al observed lower sensitivity but higher specificity of HE4 and CA125 for predicting LNM, LVSI, or MI > 50% compared to HE4 alone [ 68 ]. Only one study has reported on association of a combination of HE4 and CA125 with OS.…”

“…Bolstad et al reported that compared to women aged 20 years, the level of serum HE4 was 2%, 9%, 20%, 37%, 63% and 101% higher in women aged 40, 50, 60, 70 and 83 years, respectively [ 127 ]. Serum HE4 is also higher in postmenopausal women compared to those who are pre-menopausal [ 25 , 60 , 68 , 124 ]. However, this association may be secondary to the impact of age on HE4 levels rather than directly related to menopause.…”