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Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions
Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen; Haukeland Hosp, Dept Obstet & Gynecol, Bergen.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2018 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 148, no 1, p. 197-203Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 148, no 1, p. 197-203
Keywords [en]
Endometrial carcinoma, Hysterectomy, Prognostic, Biomarker, ASRGLI
National Category
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-343878DOI: 10.1016/j.ygyno.2017.10.025ISI: 000423139400031PubMedID: 29096882OAI: oai:DiVA.org:uu-343878DiVA, id: diva2:1189422
Available from: 2018-03-09 Created: 2018-03-09 Last updated: 2018-03-09Bibliographically approved

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Edqvist, Per-Henrik D.

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