Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions

Objective. Loss of Asparaginase-like protein 1 (ASRGLI) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGLI expression in endometrial carcinoma precursor lesion and metastases. Methods. 782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGLI expression by immunohistochemistry in relation to clinical and histopathological data. ASRGLI mRNA level was investigated in 237 primary tumors and related to survival and ASRGLI protein expression. Results. Low expression of ASRGLI protein and ASRGLI mRNA predicted poor disease specific survival (P < 0.001). In multivariate survival analyses ASRGLI had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04-2.26, P = 0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47-4.74, P = 0.001). Low ASRGLI expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGLI was lost in the majority of metastatic lesions. Conclusions. In a prospective setting ASRGLI validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma, patient population. (C) 2017 Elsevier Inc. All rights reserved.