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Gynecol Oncol. 2018 Jan;148(1):197-203. doi: 10.1016/j.ygyno.2017.10.025. Epub 2017 Oct 31.

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

Author information

1
Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
2
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala, Sweden.
3
Department of Biomedicine, University of Bergen, Bergen, Norway.
4
Department of Pathology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.
5
Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway. Electronic address: camilla.krakstad@med.uib.no.

Abstract

OBJECTIVE:

Loss of Asparaginase-like protein 1 (ASRGL1) 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 ASRGL1 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 ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. ASRGL1 mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression.

RESULTS:

Low expression of ASRGL1 protein and ASRGL1 mRNA predicted poor disease specific survival (P<0.001). In multivariate survival analyses ASRGL1 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 ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions.

CONCLUSIONS:

In a prospective setting ASRGL1 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.

KEYWORDS:

ASRGL1; Biomarker; Endometrial carcinoma; Hysterectomy; Prognostic

PMID:
29096882
DOI:
10.1016/j.ygyno.2017.10.025
[Indexed for MEDLINE]

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