Publication

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

Creemers, S. G., Feelders, R. A., Valdes, N., Ronchi, C. L., Volante, M., van Hemel, B. M., Luconi, M., Ettaieb, M. H. T., Mannelli, M., Chiara, M. D., Fassnacht, M., Papotti, M., Kerstens, M. N., Nesi, G., Haak, H. R., van Kemenade, F. J. & Hofland, L. J., Oct-2020, In : Endocrine-Related cancer. 27, 10, p. 541-550 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Creemers, S. G., Feelders, R. A., Valdes, N., Ronchi, C. L., Volante, M., van Hemel, B. M., Luconi, M., Ettaieb, M. H. T., Mannelli, M., Chiara, M. D., Fassnacht, M., Papotti, M., Kerstens, M. N., Nesi, G., Haak, H. R., van Kemenade, F. J., & Hofland, L. J. (2020). The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study. Endocrine-Related cancer, 27(10), 541-550. https://doi.org/10.1530/ERC-19-0378, https://doi.org/10.1530/ERC-19-0378

Author

Creemers, S G ; Feelders, R A ; Valdes, N ; Ronchi, C L ; Volante, M ; van Hemel, B M ; Luconi, M ; Ettaieb, M H T ; Mannelli, M ; Chiara, M D ; Fassnacht, M ; Papotti, M ; Kerstens, M N ; Nesi, G ; Haak, H R ; van Kemenade, F J ; Hofland, L J. / The IGF2 methylation score for adrenocortical cancer : an ENSAT validation study. In: Endocrine-Related cancer. 2020 ; Vol. 27, No. 10. pp. 541-550.

Harvard

Creemers, SG, Feelders, RA, Valdes, N, Ronchi, CL, Volante, M, van Hemel, BM, Luconi, M, Ettaieb, MHT, Mannelli, M, Chiara, MD, Fassnacht, M, Papotti, M, Kerstens, MN, Nesi, G, Haak, HR, van Kemenade, FJ & Hofland, LJ 2020, 'The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study', Endocrine-Related cancer, vol. 27, no. 10, pp. 541-550. https://doi.org/10.1530/ERC-19-0378, https://doi.org/10.1530/ERC-19-0378

Standard

The IGF2 methylation score for adrenocortical cancer : an ENSAT validation study. / Creemers, S G; Feelders, R A; Valdes, N; Ronchi, C L; Volante, M; van Hemel, B M; Luconi, M; Ettaieb, M H T; Mannelli, M; Chiara, M D; Fassnacht, M; Papotti, M; Kerstens, M N; Nesi, G; Haak, H R; van Kemenade, F J; Hofland, L J.

In: Endocrine-Related cancer, Vol. 27, No. 10, 10.2020, p. 541-550.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Creemers SG, Feelders RA, Valdes N, Ronchi CL, Volante M, van Hemel BM et al. The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study. Endocrine-Related cancer. 2020 Oct;27(10):541-550. https://doi.org/10.1530/ERC-19-0378, https://doi.org/10.1530/ERC-19-0378


BibTeX

@article{5b59c29062494895bde12da9392635bc,
title = "The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study",
abstract = "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 py rosequenced. 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 0.8 66-0.952). 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.",
keywords = "adrenocortical carcinoma, biomarker, DNA methylation, IGF2 methylation score, WEISS SYSTEM, EUROPEAN-SOCIETY, CARCINOMA, TUMORS, MANAGEMENT, EXPRESSION, FEATURES, NETWORK, COLLABORATION, PREVALENCE",
author = "Creemers, {S G} and Feelders, {R A} and N Valdes and Ronchi, {C L} and M Volante and {van Hemel}, {B M} and M Luconi and Ettaieb, {M H T} and M Mannelli and Chiara, {M D} and M Fassnacht and M Papotti and Kerstens, {M N} and G Nesi and Haak, {H R} and {van Kemenade}, {F J} and Hofland, {L J}",
year = "2020",
month = oct,
doi = "10.1530/ERC-19-0378",
language = "English",
volume = "27",
pages = "541--550",
journal = "Endocrine-Related cancer",
issn = "1351-0088",
publisher = "BIOSCIENTIFICA LTD",
number = "10",

}

RIS

TY - JOUR

T1 - The IGF2 methylation score for adrenocortical cancer

T2 - an ENSAT validation study

AU - Creemers, S G

AU - Feelders, R A

AU - Valdes, N

AU - Ronchi, C L

AU - Volante, M

AU - van Hemel, B M

AU - Luconi, M

AU - Ettaieb, M H T

AU - Mannelli, M

AU - Chiara, M D

AU - Fassnacht, M

AU - Papotti, M

AU - Kerstens, M N

AU - Nesi, G

AU - Haak, H R

AU - van Kemenade, F J

AU - Hofland, L J

PY - 2020/10

Y1 - 2020/10

N2 - 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 py rosequenced. 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 0.8 66-0.952). 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.

AB - 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 py rosequenced. 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 0.8 66-0.952). 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.

KW - adrenocortical carcinoma

KW - biomarker

KW - DNA methylation

KW - IGF2 methylation score

KW - WEISS SYSTEM

KW - EUROPEAN-SOCIETY

KW - CARCINOMA

KW - TUMORS

KW - MANAGEMENT

KW - EXPRESSION

KW - FEATURES

KW - NETWORK

KW - COLLABORATION

KW - PREVALENCE

U2 - 10.1530/ERC-19-0378

DO - 10.1530/ERC-19-0378

M3 - Article

C2 - 32668404

VL - 27

SP - 541

EP - 550

JO - Endocrine-Related cancer

JF - Endocrine-Related cancer

SN - 1351-0088

IS - 10

ER -

ID: 130941762