HE4 and CA125 levels in the preoperative assessment of endometrial cancer patients: a prospective multicenter study (ENDOMET)

Abstract
Objective. To evaluate whether human epididymis protein 4 (HE4) and CA125
correlate with known high-risk prognostic factors for endometrial cancer.
Design. Prospective multicenter study. Setting. Three Danish tertiary gynecological
oncology centers. Population. A total of 352 patients with endometrial cancer
and atypical endometrial hyperplasia consecutively referred between 1 September
2009 and 1 January 2012. Methods. Preoperative blood samples were obtained
from all patients. Biomarker levels were correlated with pathological characteristics
of hysterectomy specimens. Main outcome measures. FIGO stage, depth of myometrial
invasion, cervical involvement, lymph node metastases, and histological
type and grade of tumor. Results. We found that both HE4 and CA125 were significantly
positively correlated with histological grade (HE4: p = 0.002 and CA125:
p = 0.027), lymph node metastases (HE4: p = 0.013 and CA125: p < 0.0001),
myometrial invasion (p < 0.0001) and cervical involvement (p < 0.0001). Furthermore,
a significant increase was found with increasing FIGO stage for both
markers (p < 0.0001). In a combined index including age, the diagnostic value
increases. Area under the receiver operating characteristics curves were higher for
the index compared with the markers individually for all our endpoints. The
calculated plots for the combined index may assist gynecologists in predicting the
risk of deep myometrial invasion, cervical involvement and lymph node metastases.
The analyses emphasize that the combined markers should be used in the prediction
of prognostic factors. Conclusion. This study confirmed that the markers
are significantly elevated in patients with prognostic high-risk factors and may,
therefore, be used as an additional tool in combination with imaging and clinical
information when planning the treatment of endometrial cancer patients.