WomEC: a novel diagnostic test for the detection of endometrial cancer in uterine fluids

BackgroundEndometrial cancer (EC) is the first most common gynecological cancer. Abnormal uterine bleeding is the main symptom to initiate the multistep EC diagnostic process. Final diagnosis relies on the observation of tumor cells in a pipelle biopsy specimen, but this fails to diagnose up to 30% of patients leading to further invasive tests. In this study, we used the liquid fraction of pipelle biopsies -the uterine fluid- to develop an EC diagnostic test.MethodsEC diagnostic biomarkers were discovered and verified in four independent clinical case-control retrospective cohorts including 291 patients. Targeted mass spectrometry was used for protein analysis and statistical analysis permitted to develop 2 and 3-protein panels using logistic regression models. Out of the most accurate biomarkers, six proteins were validated in uterine fluids from an independent case-control retrospective cohort of 250 patients using commercial immunoassays (ELISAs). For 6 selected biomarkers, recombinant antigen and monoclonal antibodies were developed using the HybriFree technology and Octet analysis.ResultsAmong 106 proteins studied by mass spectrometry in uterine fluids from 291 patients, 58 proteins had significant EC diagnostic potential. Among those, a 3-protein panel permitted to detect EC patients with a negative predictive value of 97% (99% sensitivity, 79% specificity). We validate the diagnostic potential of 6 biomarkers in uterine fluids from 250 patients (120 EC, 130 non-EC), using a widely available immunoassay technique (adj.p-value<0.05, fold-change>2, AUC>0.70). A pair of high affinity recombinant antibodies were selected for 6 biomarkers and currently clinically relevant immunoassays are being developed.ConclusionsThis study validates the diagnostic potential of protein biomarkers to detect EC using uterine fluids. Based on these results, we are currently developing WomEC, a diagnsotic test that measures 3 biomarkers in uterine fluids to aid in the diagnosis of EC in women presenting with abnormal uterine bleeding.Legal entity responsible for the studyGroup of Biomedical Research in Gynecology, Vall Hebron Institute of Research.FundingMiMARK Diagnostics SL.DisclosureA. Gil-Moreno: Financial Interests, Personal and Institutional, Other, Inventor on a patent protecting the results derived from this study: VHIR; Financial Interests, Personal and Institutional, Stocks/Shares, MiMARK Diagnostics, S.L (which licensed the patents related to this study): MiMARK Diagnostics SL. J. Carvajal, A. Garcia, M. Marti, M. Cedo: Financial Interests, Institutional, Full or part-time Employment: MiMARK Diagnostics SL. E. Coll de la Rubia: Financial Interests, Personal and Institutional, Full or part-time Employment: MiMARK Diagnostics SL. M. Rigau: Financial Interests, Institutional, Stocks/Shares, MiMARK Diagnostics, S.L (which licensed the patents related to this study): MiMARK Diagnostics SL. E. Martinez, I. Campoy: Financial Interests, Personal and Institutional, Inventor on a patent protecting the results derived from this study: VHIR. E. Colas: Financial Interests, Personal and Institutional, Other, Inventor on a patent protecting the results derived from this study: VHIR; Financial Interests, Personal and Institutional, Stocks/Shares, MiMARK Diagnostics, S.L (which licensed the patents related to this study): MiMARK Diagnostics SL; Financial Interests, Personal and Institutional, Full or part-time Employment: MiMARK Diagnostics SL. All other authors have declared no conflicts of interest.