Michael R Clay1, Emilia M Pinto2, Lauren Fishbein3, Tobias Else4, Katja Kiseljak-Vassiliades3,5. 1. Department of Pathology, University of Colorado School of Medicine at Colorado Anschutz Medical Campus Aurora, CO, USA. 2. Department of Pathology; St. Jude Children's Research Hospital, Memphis, TN, USA. 3. Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine at Colorado Anschutz Medical Campus Aurora, CO, USA. 4. Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. 5. Research Service Veterans Affairs Medical Center, Aurora, CO, USA.
Abstract
CONTEXT: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that affects patients across the age spectrum. Although the overall survival in patients with ACC is poor, there is significant heterogeneity in terms of outcomes, presentation, and underlying genetic drivers. EVIDENCE ACQUISITION: This review is based on the evidence collected from primary research studies, expert reviews, and published guidelines. The studies were identified through PubMed search with key words "adrenocortical carcinoma," "prognosis," "pathology," and "genetics." The PubMed search was complemented by authors' expertise, research, and clinical experience in the field of ACC. EVIDENCE SYNTHESIS: Identification of biomarkers has been critical to gain better insight into tumor behavior and to guide therapeutic approach to patients. Tumor stage, resection status, and Ki67 are pathological tumor characteristics that have been identified as prognosticators in patients with ACC. Cortisol excess also correlates with worse prognosis. Clinical and histopathological characteristics help stratify patient outcomes, yet still up to 25% of patients have a different outcome than predicted. To bridge this gap, comprehensive genomic profiling studies have characterized additional profiles that correlate with clinical outcomes. In addition, studies of clinically applicable molecular markers are under way to further stratify outcomes in patients with ACC tumors. CONCLUSIONS: Clinical predictors in combination with pathological markers play a critical role in the approach to patients with ACC. Recent advances in genetic prognosticators will help extend the stratification of these tumors and contribute to a personalized therapeutic approach to patients with ACC.
CONTEXT: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that affects patients across the age spectrum. Although the overall survival in patients with ACC is poor, there is significant heterogeneity in terms of outcomes, presentation, and underlying genetic drivers. EVIDENCE ACQUISITION: This review is based on the evidence collected from primary research studies, expert reviews, and published guidelines. The studies were identified through PubMed search with key words "adrenocortical carcinoma," "prognosis," "pathology," and "genetics." The PubMed search was complemented by authors' expertise, research, and clinical experience in the field of ACC. EVIDENCE SYNTHESIS: Identification of biomarkers has been critical to gain better insight into tumor behavior and to guide therapeutic approach to patients. Tumor stage, resection status, and Ki67 are pathological tumor characteristics that have been identified as prognosticators in patients with ACC. Cortisol excess also correlates with worse prognosis. Clinical and histopathological characteristics help stratify patient outcomes, yet still up to 25% of patients have a different outcome than predicted. To bridge this gap, comprehensive genomic profiling studies have characterized additional profiles that correlate with clinical outcomes. In addition, studies of clinically applicable molecular markers are under way to further stratify outcomes in patients with ACC tumors. CONCLUSIONS: Clinical predictors in combination with pathological markers play a critical role in the approach to patients with ACC. Recent advances in genetic prognosticators will help extend the stratification of these tumors and contribute to a personalized therapeutic approach to patients with ACC.
Authors: Siyuan Zheng; Andrew D Cherniack; Ninad Dewal; Richard A Moffitt; Ludmila Danilova; Bradley A Murray; Antonio M Lerario; Tobias Else; Theo A Knijnenburg; Giovanni Ciriello; Seungchan Kim; Guillaume Assie; Olena Morozova; Rehan Akbani; Juliann Shih; Katherine A Hoadley; Toni K Choueiri; Jens Waldmann; Ozgur Mete; A Gordon Robertson; Hsin-Ta Wu; Benjamin J Raphael; Lina Shao; Matthew Meyerson; Michael J Demeure; Felix Beuschlein; Anthony J Gill; Stan B Sidhu; Madson Q Almeida; Maria C B V Fragoso; Leslie M Cope; Electron Kebebew; Mouhammed A Habra; Timothy G Whitsett; Kimberly J Bussey; William E Rainey; Sylvia L Asa; Jérôme Bertherat; Martin Fassnacht; David A Wheeler; Gary D Hammer; Thomas J Giordano; Roel G W Verhaak Journal: Cancer Cell Date: 2016-05-09 Impact factor: 31.743
Authors: Nikita Pozdeyev; Lauren Fishbein; Laurie M Gay; Ethan S Sokol; Ryan Hartmaier; Jeffrey S Ross; Sourat Darabi; Michael J Demeure; Adwitiya Kar; Lindsey J Foust; Katrina Koc; Daniel W Bowles; Stephen Leong; Margaret E Wierman; Katja Kiseljak-Vassiliades Journal: Endocr Relat Cancer Date: 2021-08-16 Impact factor: 5.900
Authors: J P Luton; S Cerdas; L Billaud; G Thomas; B Guilhaume; X Bertagna; M H Laudat; A Louvel; Y Chapuis; P Blondeau Journal: N Engl J Med Date: 1990-04-26 Impact factor: 91.245
Authors: D Malkin; F P Li; L C Strong; J F Fraumeni; C E Nelson; D H Kim; J Kassel; M A Gryka; F Z Bischoff; M A Tainsky Journal: Science Date: 1990-11-30 Impact factor: 47.728