Molecular markers for malignancy in adrenocortical tumors
Abstract
Little is known about the pathophysiology of sporadic adrenocortical tumors. Benign and malignant adrenocortical tumors are often difficult to distinguish by conventional histology. We tested 38 adrenocortical tumors (23 benign and 15 malignant) for loss of heterozygosity (LOH) at 17p13 and abnormalities in the 11p15 region (uniparental disomy, UPD, and overexpression of the IGF II gene). We showed that 17p13 LOH, 11p15 UPD and overexpression of the IFG II gene are frequent in adrenocortical tumors, occurring in 40% of them. These genetic changes are associated with the malignant phenotype and thus could be used for diagnostic evaluation of adrenocortical tumors.
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There is no overlap of LOH and mutations in the same tumors.
“Of note, there was no overlap of LOH and mutations in the same tumors.”
From Adrenocortical carcinoma (2014) · cites this paper as [203]
Examination of TP53 in 89 adrenal tumors revealed LOH at 17p13 in 11 of 13 ACCs and 23 of 76 ACAs.
“Examination of TP53 in 89 adrenal tumors revealed loss of heterozygosity (LOH) at the 17p13 in 11 of 13 ACCs and 23 of 76 ACAs (203).”
From Adrenocortical carcinoma (2014) · cites this paper as [203]
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Else, T., Kim, A. C., Sabolch, A., Raymond, V. M., Kandathil, A., Caoili, E. M., Jolly, S., Miller, B. S., Giordano, T. J., & Hammer, G. D. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1029 · Cited by 892 · see citing works
Seccia, T. M., Fassina, A., Nussdorfer, G. G., Pessina, A. C., & Rossi, G. P. (2005) · Endocrine Related Cancer · doi:10.1677/erc.1.00867 · Cited by 131 · see citing works
Emerging Treatment Strategies for Adrenocortical Carcinoma: A New Hope
Kirschner, L. S. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1739 · Cited by 110 · see citing works
“Both studies determined that up-regulation of IGF-II expression was the dominant change, confirming previous observations (37, 38).”
ResultAnalysis of Genomic Alterations in Sporadic Adrenocortical Lesions
Zhao, J., Speel, E. M., Muletta-Feurer, S., Rütimann, K., Saremaslani, P., Roth, J., Heitz, P. U., & Komminoth, P. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65205-4 · Cited by 104 · see citing works
“9,24 The contradictory data between CGH and FISH observed in tumors 33 and 39 (Table 1) may be due to intratumoral heterogeneity.”
BackgroundHerr, I., Wilhelm, D., B�hler, T., Angel, P. E., & Debatin, K. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990129)80:3 · Cited by 40 · see citing works
Wilkin, F., Gagné, N., Paquette, J., Oligny, L. L., & Deal, C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.5.6589 · Cited by 99 · see citing works
Guillaud-Bataille, M., Ragazzon, B., de Reyniès, A., Chevalier, C., Francillard, I., Barreau, O., Steunou, V., Guillemot, J., Tissier, F., Rizk‐Rabin, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103744 · Cited by 52 · see citing works
“We identified pUPD in most IGF2-high ACC of our series; these samples showed the expected methylation profiles at ICR1 and ICR2 (80% of the tumors) and the expression of the five imprinted genes at this loci differed as expected from their expression in ACA.”
BackgroundInfluentialSelf-citationPinto, E. M., Galindo, C. R., Pounds, S. B., Wang, L., Clay, M. R., Neale, G. A. M., Garfinkle, E. A. R., Lam, C. G., Levy, C. F., Pappo, A. S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.2460 · Cited by 51 · see citing works
“001 Virilization alone 23 (38) 32 (59) Virilization plus cushing 10 (17) 17 (31) Cushing alone 12 (20) 0 (0) No clinical signs 12 (20) 3 (6) Aldosterone-producing tumor 3 (5) 1 (2) Aldosterone plus cushing 0 (0) 1 (2) Tumor histology .”
Soon, P. S. H., Libé, R., Benn, D. E., Gill, A. J., Shaw, J., Sywak, M. S., Groussin, L., BERTAGNA, X. Y., Gicquel, C., Bertherat, J. Y., et al. (2008) · Annals of Surgery · doi:10.1097/sla.0b013e318153ff55 · Cited by 48 · see citing works
“Hyperestrogenism (%) 1 (5) — 1 (7) 1 (10) —”
Self-citationLuciani, P., Ferruzzi, P., Arnaldi, G., Crescioli, C., Benvenuti, S., Nesi, G., Valeri, A., Greeve, I., Serio, M., Mannelli, M., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031065 · Cited by 45 · see citing works
Mannelli, M., Gelmini, S., Arnaldi, G., Becherini, L., Bemporad, D., Crescioli, C., Pazzagli, M., Mantero, F., Serio, M., & Orlando, C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.1.6300 · Cited by 39 · see citing works
“More recently, several cytological characteristics, such as the expression of the proliferating cell antigen (17), of the adrenal 4 binding protein (18), of the c-Myc protein (19), of the insulin-like growth factor II gene (20), or of the p53 protein (21) or the DNA index (19, 22), have been evaluated as indexes of ma…”
BackgroundMcNicol, A. M. (2008) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2008-132-1263-lotac · Cited by 28 · see citing works
Genetic background of adrenocortical tumor development
Kjellman, M., Larsson, C., & Bäckdahl, M. (2001) · World Journal of Surgery · doi:10.1007/s00268-001-0034-3 · Cited by 27 · see citing works
“ACT have been shown to be only slightly increased, and IGF2 expression therefore has been suggested as a marker for malignancy [ 67 ].”
BackgroundThe role of epithelial growth factors and insulin growth factors in the adrenal neoplasms
Angelousi, A. G., Kyriakopoulos, G., Ansari, N. N., Karageorgou, M., & Kassi, E. N. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.05.52 · Cited by 23 · see citing works
“In most of cases, this overexpression has been associated with DNA demethylation at IGF-2 locus, and paternal isodisomy (23,41) albeit not with tumor behavior and clinical prognosis (42).”
BackgroundA Diagnostic Approach to Adrenal Cortical Lesions
McNicol, A. M. (2008) · Endocrine Pathology · doi:10.1007/s12022-008-9055-x · Cited by 24 · see citing works
“Adrenal carcinoma is associated with overexpression of IGF-II [32, 33] which can be detected by immunohistochemistry.”
BackgroundBeltsevich, D. G., Mel'nichenko, G. A., Kuznetsov, N. S., Troshina, E. A., Platonova, N. M., Vanushko, V. E., Yukina, M. Y., & Молашенко, Н. В. (2016) · Endocrine Surgery · doi:10.14341/serg2016431-42 · Cited by 21 · see citing works
Telomerase activity in the differentiation of benign and malignant adrenal tumors
Teng, L., Tucker, O., Malchoff, C. D., Vaughan, E. D., Jacobson, J., & Fahey, T. J. (1998) · Surgery · doi:10.1067/msy.1998.92172 · Cited by 18 · see citing works
Federal clinical practice guidelines on the diagnostics and treatment of adrenocortical cancer
Mel'nichenko, G. A., Stilidi, I. S., Alekseev, B. Y., Gorbunova, V. A., Beltsevich, D. G., Райхман, А. О., Kuznetsov, N. S., Zhukov, N. V., & Bokhyan, V. Y. (2014) · Problems of Endocrinology · doi:10.14341/probl201460251-67 · Cited by 17 · see citing works
Classification of adrenal cortical tumors: Promise of the ‘molecular’ approach
Giordano, T. J. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.10.012 · Cited by 8 · see citing works
Lerário, A. M., Mendonca, B. B., & Lin, C. J. (2005) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302005000500016 · Cited by 4 · see citing works
Expression of telomerase (hTERT) in aldosterone-producing adrenocortical tumors
Sticchi, D., Fassina, A., Ganzaroli, C., Pasqualetto, C., Pessina, A., Nussdorfer, G. G., & Rossi, G. P. (2006) · International Journal of Molecular Medicine · doi:10.3892/ijmm.17.3.469 · Cited by 3 · see citing works
Cellular and Molecular Pathology of Adrenocortical Carcinoma
Else, T. (2009) · Springer eBooks · doi:10.1007/978-0-387-77236-3_9 · Cited by 1 · see citing works
“Gicquel et al. showed that LOH at 17p13 was present in 11 of 13 ACC and 23 of 76 ACA [ 28 ].”
BackgroundDraft of Russian Guidelines of Diagnosis and Treatment of Adrenal Cortical Cancer
Mel'nichenko, G. A., Stilidi, I. S., Горбунова, В. А., Alexeev, B. Y., Beltsevich, D. G., Райхман, А. О., Kuznetsov, N. S., Zhukov, N. V., & Bokhyan, V. Y. (2014) · Endocrine Surgery · doi:10.14341/serg201414-26 · Cited by 1 · see citing works
“Проанализированы ДНК надпочечниковых опухолей при спорадическом АКР в участках 17p (содержащем TP53-ген) и в 11p15 (содержащим IGF-2/CDKN1C) [5].”
Aldosterone-Producing Adrenocortical Carcinoma
Patalano, A., Cicala, M. V., & Mantero, F. (2009) · Springer eBooks · doi:10.1007/978-0-387-77236-3_27
“Although several criteria have been proposed to allow discrimination between benign and malignant tumors [30], including some molecular markers such as the DNA index [30, 31], the expression of proliferating cell nuclear antigen (PCNA) [32], p53 protein [33], steroidogenic factor 1 [34], c-Myc protein [31], or insulin…”
BackgroundNew Strategies for the Treatment of Adrenocortical Carcinoma
Kirschner, L. S. (2009) · Springer eBooks · doi:10.1007/978-0-387-77236-3_30
“This observation paralleled earlier studies of IGF2 signaling done in isolation [9, 10].”
ResultGATA TRANSCRIPTION FACTORS IN THE DEVELOPMENT AND TUMORS OF THE ADRENAL CORTEX
Kiiveri, S. (2004) · Työväentutkimus Vuosikirja
Importância da via do mevalonato nas neoplasias do córtex adrenal
Valassi, H. P. L. (2011) · doi:10.11606/t.5.2011.tde-18022011-122810
Diagnosis of adrenocortical cancer
Mel'nichenko, G. A., Stilidi, I. S., Alekseev, B. Y., Beltsevich, D. G., Райхман, А. О., Kuznetsov, N. S., Zhukov, N. V., & Bokhyan, V. Y. (2014) · P A Herzen Journal of Oncology · doi:10.17116/oncolog2014690-94
Beltsevich, D. G., Russian Federation, & Russian, B. (2014) · CyberLeninK (CyberLeninka)
Диагностика адренокортикального рака
StiliDi, S., Kuznetsov, S. G., & Sechenov, M. (2014)
McNicol, A. M. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-396-1_8
- Authors
- Gicquel, C., & Le Bouc, Y.
- Affiliations
- Hôpital Armand-Trousseau (FR)
- Venue
- Hormone Research
- Publisher
- S. Karger AG
- Published
- 2008-12-09
- Volume
- 47
- Issue
- 4-6
- Pages
- 269-272
- ISSN
- 0301-0163 (ISSN-L)
- 1423-0046
- OpenAlex
- W2000715156
- Cited by
- 35
- References
- 0
- Citations by year
- 2018: 1 · 2017: 1 · 2016: 1 · 2014: 7 · 2013: 1
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- adrenocortical tumors, adrenocortical carcinoma, loss of heterozygosity, 17p13, 11p15, uniparental disomy, IGF2 overexpression, benign versus malignant differentiation, tumor diagnosis
- MeSH terms
- Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Alleles, Chromosome Aberrations, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 17, Female, Heterozygote, Humans, Insulin-Like Growth Factor II, Male, Middle Aged, RNA, Messenger, Gene Expression
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