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High AGR2 protein is a feature of low grade endometrial cancer cells

BACKGROUND: Biomarkers for identification of endometrial cancers (ECs) with high risk of recurrence are required to reduce the rising EC-related mortality. AGR2 is a prognostic marker in several hormonally-regulated cancers. AIM: To assess the utility of AGR2 as a prognostic marker in EC. METHODS: A...

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Detalles Bibliográficos
Autores principales: Kamal, Areege, Valentijn, Anthony, Barraclough, Roger, Rudland, Philip, Rahmatalla, Nihad, Martin-Hirsch, Pierre, Stringfellow, Helen, Decruze, Shandya B., Hapangama, Dharani K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101135/
https://www.ncbi.nlm.nih.gov/pubmed/30140383
http://dx.doi.org/10.18632/oncotarget.25838
Descripción
Sumario:BACKGROUND: Biomarkers for identification of endometrial cancers (ECs) with high risk of recurrence are required to reduce the rising EC-related mortality. AGR2 is a prognostic marker in several hormonally-regulated cancers. AIM: To assess the utility of AGR2 as a prognostic marker in EC. METHODS: AGR2 immunoexpression was evaluated in 163 human endometrial samples. Change in AGR2 mRNA levels in response to oestrogen and dihydrotestosterone was studied in vitro. RESULTS: Upregulation of AGR2 (protein and mRNA) was seen in low grade EC, compared to the postmenopausal endometrium (P = 0.013) and to the high-grade EC (P < 0.0001). Elevated AGR2 protein expression-scores were associated with a high expression of estrogen alpha (ERα), progesterone, androgen receptors and early clinical stages. Metastatic lesions maintained higher AGR2 expression relative to matched-primary tumors. High-AGR2 protein levels were associated with better overall survival (P = 0.02) in all ECs, but in highly-ERα-expressing ECs, AGR2 associated with unfavourable patient outcome. Androgen through its receptor, downregulated AGR2 mRNA in the Ishikawa cells. CONCLUSIONS: AGR2 is overexpressed in low grade ECs and positively associated with hormone receptors. The association between high AGR2 and progressive disease within the high-ERα-expressing ECs suggests that in this group of patients, AGR2 might be a potential biomarker of poor prognosis.