Prognostic Role of Targeted Methylation Analysis in Paraffin-embedded Samples of Adrenocortical Carcinoma.
J Clin Endocrinol Metab
; 107(10): 2892-2899, 2022 09 28.
Article
en En
| MEDLINE
| ID: mdl-35929659
ABSTRACT
CONTEXT Adrenocortical carcinoma (ACC) is a rare aggressive disease with heterogeneous prognoses. Previous studies identified hypermethylation in the promoter region of specific genes to be associated with poor clinical outcome. OBJECTIVE:
Comparative analysis of promising hypermethylated genes as prognostic markers and evaluation of their added value to established clinical prognostic tools.DESIGN:
We included 237 patients with ACCs. Tumor DNA was isolated from formalin-fixed paraffin-embedded (FFPE) samples. Targeted pyrosequencing was used to detect promoter region methylation in 5 preselected genes (PAX5, GSTP1, PYCARD, PAX6, G0S2). The prognostic role of hypermethylation pattern was compared with the Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score. Primary endpoints were progression-free (PFS) and overall survival (OS), with disease-free (DFS) as secondary endpoint.RESULTS:
A total of 27.9%, 13.9%, 49%, 49%, and 25.3% of cases showed hypermethylation in PAX5, GSTP1, PYCARD, PAX6, and G0S2, 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, only hypermethylation of PAX5 remained significantly associated with OS (Pâ =â 0.013; HRâ =â 1.95, 95% CI, 1.2-3.3) in multivariable analysis. A model for risk stratification was developed, combining PAX5 methylation status and S-GRAS groups, showing improved prognostic performance compared to S-GRAS alone (Harrell's C index OSâ =â 0.751, PFSâ =â 0.711, DFSâ =â 0.688).CONCLUSIONS:
This study demonstrated that hypermethylation in PAX5 is associated with worst clinical outcome in ACC, even after accounting for S-GRAS score. Assessing methylation in FFPE material is straightforward in the clinical setting and could be used to improve accuracy of prognostic classification, enabling the direction of personalized management.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Corteza Suprarrenal
/
Carcinoma Corticosuprarrenal
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania