ECE2022 Poster Presentations Endocrine-Related Cancer (41 abstracts)
Prognostic role of targeted methylation analysis in formalin-fixed paraffin-embedded samples of adrenocortical carcinoma
Juliane Lippert 1 , Barbara Altieri 1 , Breanna Morrison 2 , Sonja Steinhauer 1 , Gabrielle Smith 3 , Antonia Lorey 1 , Urlaub Hanna 1 , Stefan Kircher 4 , Alice J Sitch 2 , Martin Fassnacht 1 & Cristina Ronchi 1,3
1Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany; 2Institute of Applied Health Research, University of Birmingham, United Kingdom; 3Institute of Metabolism and System Research, University of Birmingham, United Kingdom; 4Institute of Pathology, University of Wuerzburg, Germany
Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine neoplasia with heterogeneous molecular background and clinical outcome. Previous studies identified hypermethylation in specific genes to be associated with poor prognosis. Here, we aimed to investigate the role of methylation pattern for prognostic stratification of patients with ACC as compared to clinical parameters, using methods easily applicable in clinical routine. We investigated a total of 237 ACCs (96 M/141F); data were obtained from a previously published retrospective cohort (n=107, Lippert et al 2018) with updated follow up data (median overall survival (OS)=65 months) and a novel independent cohort (n=130, median OS=53 months). Tumour-DNA was isolated from formalin-fixed paraffin-embedded specimens. Leukocyte-DNA was used as reference. Targeted pyrosequencing or Deep Bisulfite Sequencing was used to detect methylation in the promoter region of 5 selected genes (G0S2, GSTP1, PAX5, PAX6, and PYCARD). Genes were considered “hypermethylated” if percentage values were >25%. Clinical and histological parameters were collected for S-GRAS score calculation as previously published (Elhassan et al 2021). Survival analysis was performed for progression-free survival (PFS) and OS. A Cox survival model was applied to test the prognostic impact of hypermethylation in each gene and S-GRAS score, separately and combined. Analyses were also adjusted for cohorts. A total of 25%, 14%, 28%, 49% and 49% cases showed hypermethylation in G0S2, GSTP1, PAX5, PAX6, and PYCARD, respectively. Hypermethylation in all individual genes – except GSTP1 - was significantly associated with both PFS and OS with Hazard Ratios (HR) between 1.4 and 2.3. However, overall the models did not perform well. In the model combining methylation of all genes and S-GRAS score, hypermethylation of PAX5 was the only molecular parameter significantly and independently related to OS (HR=1.9, 95%CI 1.2-3.2). As a comparison, the best HRs for OS were obtained for S-GRAS score group 2 and 3 were 4.5 and 6.8, respectively, when compared to an S-GRAS score group 0.
In conclusion, this study confirms that hypermethylation in preselected genes is significantly associated with worst PFS and OS in ACC. However, only hypermethylation in PAX5 was related to OS when accounting for S-GRAS score. Assessing targeted methylation is straightforward and feasible in the clinical setting. Therefore, the addition of methylation status of PAX5 in the baseline evaluation of ACC patients could help to improve accuracy of prognostic classification and enable the direction of personalized management.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more