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Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma

Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma

Authors :
Joël Coste
Antoine Tabarin
Karine Perlemoine
Louis Jacob
Ronald R. de Krijger
Simon Garinet
Jens Waldmann
Olivier Chabre
Mathilde Sibony
Felix Beuschlein
Magalie Haissaguerre
Bertrand Dousset
Nadim Hamzaoui
Bruno de La Villéon
Bruno Ragazzon
Anne Jouinot
Laurence Amar
Martin Fassnacht
Esther Korpershoek
Massimo Mannelli
Xavier Bertagna
Rossella Libé
Marcus Quinkler
Frédérique Tissier
Guillaume Assié
Jérôme Bertherat
Matthias Kroiss
Julien Sakat
Lionel Groussin
Eric Baudin
Michaela Luconi
Cristina L Ronchi
Silviu Sbiera
Mario Neou
Sébastien Gaujoux
Pathology
Source :
JAMA Oncology, 5(10), 1440. American Medical Association, JAMA Oncol, JAMA Oncology, 5(10), 1440-1447. American Medical Association
Publication Year :
2019

Abstract

IMPORTANCE: The risk stratification of adrenocortical carcinoma (ACC) based on tumor proliferation index and stage is limited. Adjuvant therapy after surgery is recommended for most patients. Pan-genomic studies have identified distinct molecular groups closely associated with outcome. OBJECTIVE: To compare the molecular classification for prognostic assessment of ACC with other known prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective biomarker analysis, ACC tumor samples from 368 patients who had undergone surgical tumor removal were collected from March 1, 2005, to September 30, 2015 (144 in the training cohort and 224 in the validation cohort) at 21 referral centers with a median follow-up of 35 months (interquartile range, 18-74 months). Data were analyzed from March 2016 to March 2018. EXPOSURES: Meta-analysis of pan-genomic studies (transcriptome, methylome, chromosome alteration, and mutational profiles) was performed on the training cohort. Targeted biomarker analysis, including targeted gene expression (BUB1B and PINK1), targeted methylation (PAX5, GSTP1, PYCARD, and PAX6), and targeted next-generation sequencing, was performed on the training and validation cohorts. MAIN OUTCOMES AND MEASURES: Disease-free survival. Cox proportional hazards regression and C indexes were used to assess the prognostic value of each model. RESULTS: Of the 368 patients (mean [SD] age, 49 [16] years), 144 were in the training cohort (100 [69.4%] female) and 224 were in the validation cohort (142 [63.4%] female). In the training cohort, pan-genomic measures classified ACC into 3 molecular groups (A1, A2, and A3-B), with 5-year survival of 9% for group A1, 45% for group A2, and 82% for group A3-B (log-rank P

Details

Language :
English
ISSN :
23742437
Database :
OpenAIRE
Journal :
JAMA Oncology, 5(10), 1440. American Medical Association, JAMA Oncol, JAMA Oncology, 5(10), 1440-1447. American Medical Association
Accession number :
edsair.doi.dedup.....0b5ac73c5024050e6263ed05b3877800