Abstract
Background: The purpose of this study was to assess the diagnostic and prognostic impact of preoperative serum determination of human epididymis protein 4 (sHE4), and to investigate its potential correlation with clinicopathological features and survival endpoints in endometrial cancer patients.
Methods: Preoperative serum samples from 193 endometrial cancer patients and 125 women with normal endometrium were measured for sHE4 and serum CA125 (sCA125) concentrations by quantitative chemiluminescent microparticle immunoassays on the automated Architect instrument.
Results: sHE4 concentrations were significantly higher in endometrial cancer patients regardless of tumour stage and grade compared with normal controls. Setting the specificity at 95%, the sensitivities in detecting endometrial cancer patients were 66% for HE4, 33% for CA125 and 64% for the combination of the two markers. High concentrations of both HE4 and CA125 significantly correlated with all clinicopathological features characterising a more aggressive tumour phenotype. In multivariate analysis, only high preoperative sHE4 concentrations, but not sCA125, were independent prognostic factors for shorter Overall Survival, Disease-Free Survival and Progression-Free Survival.
Conclusions: HE4 is more sensitive and specific than CA125 in distinguishing endometrial cancer patients from women with normal endometrium, regardless of tumour stage and grade. sHE4 appears to be associated with a more aggressive tumour variant and it could be clinically useful, in identifying high-risk endometrial cancer patients, for a tailored surgical and postoperative therapy. HE4 significant correlation with decreased Overall Survival, Disease Free Survival and Progression Free Survival suggests its potential role as a novel prognostic marker for endometrial cancer.
We wish to thank all the nurses working in the Department of Obstetrics and Gynaecology of the University of Brescia and especially Ms. Margherita Franzoni, for the assistance in collecting blood samples. We are also grateful to Ms. Michela Faustini for her essential technical contribution in performing the Architect assays and to Ms. Ilary Toresini for informatic support. This investigation was supported by the grant from the ‘Istituto Superiore di Sanità’ (Programma Italia-USA “Farmacogenomica Oncologica”, convenzione 527/B4/4), Rome, Italy.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding and employment played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: Dr. Antonella Ravaggi was invited for a presentation as an expert testimony to a workshop sponsored by Abbott Diagnostics at the ISOBM congress in October 2011.
Employment or leadership: Dr. Claudio Galli is currently employed by Abbott Diagnostics as the Scientific Affairs Manager, Italy.
Honorarium: None declared.
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