The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study

in Endocrine-Related Cancer
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  • 1 Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  • 2 Servicio de Endocrinología y Nutrición, Hospital Universitario de Asturias, Oviedo, Spain
  • 3 Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany
  • 4 Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
  • 5 Department of Oncology, University of Turin, Orbassano, Turin, Italy
  • 6 Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • 7 Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, Florence, Italy
  • 8 Departments of Internal Medicine and Endocrinology, Máxima Medical Center, Eindhoven, The Netherlands
  • 9 Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain
  • 10 Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
  • 11 Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • 12 Division of Pathological Anatomy, University of Florence, Florence, Italy
  • 13 Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence should be addressed to L J Hofland: l.hofland@erasmusmc.nl
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Adrenocortical carcinoma (ACC) is diagnosed using the histopathological Weiss score (WS), but remains clinically elusive unless it has metastasized or grows locally invasive. Previously, we proposed the objective IGF2 methylation score as diagnostic tool for ACC. This multicenter European cohort study validates these findings. Patient and tumor characteristics were obtained from adrenocortical tumor patients. DNA was isolated from frozen specimens, where after DMR2, CTCF3, and H19 were pyrosequenced. The predictive value of the methylation score for malignancy, defined by the WS or metastasis development, was assessed using receiver operating characteristic curves and logistic and Cox regression analyses. Seventy-six ACC patients and 118 patients with adrenocortical adenomas were included from seven centers. The methylation score and tumor size were independently associated with the pathological ACC diagnosis (OR 3.756 95% CI 2.224–6.343; OR 1.467 95% CI 1.202–1.792, respectively; Hosmer–Lemeshow test P = 0.903), with an area under the curve (AUC) of 0.957 (95% CI 0.930–0.984). The methylation score alone resulted in an AUC of 0.910 (95% CI 0.866–0.952). Cox regression analysis revealed that the methylation score, WS and tumor size predicted development of metastases in univariate analysis. In multivariate analysis, only the WS predicted development of metastasis (OR 1.682 95% CI 1.285–2.202; P < 0.001). In conclusion, we validated the high diagnostic accuracy of the IGF2 methylation score for diagnosing ACC in a multicenter European cohort study. Considering the known limitations of the WS, the objective IGF2 methylation score could potentially provide extra guidance on decisions on postoperative strategies in adrenocortical tumor patients.

 

      Society for Endocrinology

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