Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study

This study aims to investigate the correlation between preoperative human epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal cutoff for stage prediction. All EC patients, treated within January 2009 and February 2014 at the Division of Gynaecologic Oncology of the University Campus Bio-Medico of Rome, were considered for the study. For the first part of the study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4 levels. In the second part of the study, the logistic regression was performed in stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred thirty-two patients with surgically staged EC and preoperative HE4 dosage were included in the study. We found that higher HE4 levels correlate with undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and 100 % of patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4 levels above the standard cutoff of 70 pmol/L. Based on receiver operating characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3 pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2 pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3 pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6 pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and 203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %). Our results suggest a potential role of HE4 in EC stage prediction.