Performance of DNA-based biomarkers for classification of adrenocortical carcinoma: a prognostic study.

Autor:	Lippert J; Division of Endocrinology and Diabetes, University Hospital of Würzburg, 97080 Würzburg, Germany., Dischinger U; Division of Endocrinology and Diabetes, University Hospital of Würzburg, 97080 Würzburg, Germany., Appenzeller S; Core Unit Bioinformatics, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, 97078 Würzburg, Germany., Prete A; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B152TT, United Kingdom.; Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham B152TT, United Kingdom.; NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham B152TT, United Kingdom., Kircher S; Department of Pathology, University of Würzburg, 97078 Würzburg, Germany., Skordilis K; Department of Histopathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B152GW, United Kingdom., Elhassan YS; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B152TT, United Kingdom.; Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham B152TT, United Kingdom., Altieri B; Division of Endocrinology and Diabetes, University Hospital of Würzburg, 97080 Würzburg, Germany., Fassnacht M; Division of Endocrinology and Diabetes, University Hospital of Würzburg, 97080 Würzburg, Germany.; Comprehensive Cancer Centre Mainfranken (CCCM), University of Würzburg, 97078 Würzburg, Germany.; Central Labor, University Hospital of Würzburg, 97080 Würzburg, Germany., Ronchi CL; Division of Endocrinology and Diabetes, University Hospital of Würzburg, 97080 Würzburg, Germany.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B152TT, United Kingdom.; Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham B152TT, United Kingdom.
Jazyk:	angličtina
Zdroj:	European journal of endocrinology [Eur J Endocrinol] 2023 Aug 02; Vol. 189 (2), pp. 262-270.
DOI:	10.1093/ejendo/lvad112
Abstrakt:	Objective: Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with heterogeneous clinical outcomes. Recent studies proposed a combination of clinical/histopathological parameters (S-GRAS score) or molecular biomarkers (BMs) to improve prognostication. We performed a comparative analysis of DNA-based BMs by evaluating their added prognostic value to the S-GRAS score. Design and Methods: A total of 194 formalin-fixed, paraffin-embedded (FFPE) ACC samples were analysed, including a retrospective training cohort (n = 107) and a prospective validation cohort (n = 87). Targeted DNA sequencing and pyrosequencing were used to detect somatic single-nucleotide variations in ACC-specific genes and methylation in the promoter region of paired box 5 (PAX5). The European Network for the Study of Adrenocortical Tumors (ENSAT) tumour stage, age, symptoms at presentation, resection status, and Ki-67 were combined to calculate S-GRAS. Endpoints were overall (OS), progression-free (PFS), and disease-free survival (DFS). Prognostic role was evaluated by multivariable survival analysis and their performance compared by Harrell's concordance index (C index). Results: In training cohort, an independent prognostic role was confirmed at multivariate analysis for two DNA-based BMs: alterations in Wnt/β-catenin and Rb/p53 pathways and hypermethylated PAX5 (both P< .05 for PFS and DFS, hazard ratio [HR] 1.47-2.33). These were combined to S-GRAS to obtain a combined (COMBI) score. At comparative analysis, the best discriminative prognostic model was COMBI score in both cohorts for all endpoints, followed by S-GRAS score (C index for OS 0.724 and 0.765, PFS 0.717 and 0.670, and DFS 0.699 and 0.644, respectively). Conclusions: Targeted DNA-based BM evaluated on routinely available FFPE samples improves prognostication of ACC beyond routinely available clinical and histopathological parameters. This approach may help to better individualise patient's management. Competing Interests: Conflict of interest: The authors declare no potential conflict of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu