ESR1 overexpression is a biomarker of relapse and worse prognosis in stage I endometrioid endometrial carcinoma

Endometrial cancer (EC) is the most common pelvic gynecologic malignancy in developed countries, and its incidence is also increasing in developing countries. Endometrioid endometrial carcinoma (EEC) is the most frequent subtype. EEC is often associated with favorable clinicopathological features and a good prognosis, especially when diagnosed in stage I. Although some patients have no signs to predict locally advanced or metastatic disease, they may present tumor relapse in the future. There is no biomarker capable of predicting the relapse of stage I EEC. The present study applied a transcriptome analysis to identify differentially expressed genes in stage I EEC, comparing relapsed with non-relapsed tumors. The estrogen receptor 1 gene (ESR1) was overexpressed in EEC stage I samples from patients who developed relapse by 4.3-fold compared to non-relapsed tumors. Subsequently, an independent set of 64 stage I EEC samples was used to validate ESR1 gene overexpression in relapsed tumors and assess estrogen receptor alpha (ERα) protein levels. ESR1 was confirmed to be overexpressed in samples from relapsed tumors, and its expression level was an independent prognostic variable for disease-free (hazard ratio=7.25) and overall survival (hazard ratio=5.15). In contrast, Erα did not show different values between relapsed and non-relapsed tumors. We concluded that ESR1 overexpression is a biomarker for poor prognosis in stage I EEC.