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Adrenocortical Carcinoma pp 127–150Cite as

Cellular and Molecular Pathology of Adrenocortical Carcinoma

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Abstract

Information molecular and genetic alterations as well as about morphological stages of adrenocortical tumorigenesis is sparse in comparison with our understanding of the development of more common neoplasms like those arising in breast or colon tissue. Breast and colon cancer have well-defined pre-cancerous or cancerous precursor lesions, carcinoma in situ, and adenoma, respectively. Stages and related genetic and epigenetic alterations are well defined. In contrast, adrenocortical tumorigenesis is less well defined. It is still a matter of debate whether adrenocortical carcinomas (ACCs) arise from normal tissue via the stages of hyperplasia or adenoma. It is certainly known that some hereditary diseases predispose to the development of ACC and, in fact, some of the alterations caused by these genetic syndromes can also be found in sporadic ACCs (see Chapter 10). The contributions of p53, IGF2, and WNT/β-catenin signaling pathway to adrenocortical tumorigenesis are discussed in chapters in this book dedicated to hereditary syndromes and their underlying genetic changes. This chapter will focus on the contributions of other known or suggested pathways, genomic and genetic alterations, as well as common principles of carcinogenesis, such as aneuploidy and clonal origin.

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References

  1. Fialkow PJ (1976) Clonal origin of human tumors. Biochim Biophys Acta 458(3):283–321

    PubMed  CAS  Google Scholar 

  2. Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190:372–373

    Article  PubMed  CAS  Google Scholar 

  3. Gicquel C (1994) Clonal analysis of human adrenocortical carcinomas and secreting adenomas. Clin Endocrinol (Oxf) 40(4):465–477

    Article  CAS  Google Scholar 

  4. Beuschlein F (1994) Clonal composition of human adrenocortical neoplasms. Cancer Res54(18):4927–4932

    PubMed  CAS  Google Scholar 

  5. Diaz-Cano SJ (2000) Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex. Am J Pathol 156(1):311–319

    PubMed  CAS  Google Scholar 

  6. Blanes A, Diaz-Cano SJ (2006) DNA and kinetic heterogeneity during the clonal evolution of adrenocortical proliferative lesions. Hum Pathol 37(10):1295–1303

    Article  PubMed  CAS  Google Scholar 

  7. Hansemann DP (1891) Ueber Pathologische Mitosen. Arch Pathol Anat Phys Klin Med 119:299–326

    Google Scholar 

  8. Boveri T (1914) Zur Frage der Entstehung maligner Tumoren. Fischer, Jena

    Google Scholar 

  9. Hardy PA, Zacharias H (2005) Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors. Cell Biol Int 29(12):983–992

    Article  PubMed  Google Scholar 

  10. Holland AJ, Cleveland DW (2009) Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat Rev Mol Cell Biol 10(7):478–487

    Article  PubMed  CAS  Google Scholar 

  11. Klein FA (1985) Flow cytometric determinations of ploidy and proliferation patterns of adrenal neoplasms: an adjunct to histological classification. J Urol 134(5):862–826

    Google Scholar 

  12. Bowlby LS et al (1986) Flow cytometric analysis of adrenal cortical tumor DNA. Relationship between cellular DNA and histopathologic classification. Cancer 58(7):1499–1505

    Article  PubMed  CAS  Google Scholar 

  13. Amberson JB (1987) Flow cytometric analysis of nuclear DNA from adrenocortical neoplasms. A retrospective study using paraffin-embedded tissue. Cancer 59(12):2091–2095

    Article  PubMed  CAS  Google Scholar 

  14. Cibas ES (1990) Cellular DNA profiles of benign and malignant adrenocortical tumors. Am J Surg Pathol 14(10):948–955

    Article  PubMed  CAS  Google Scholar 

  15. Takehara K (2005) Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistry. Int J Urol 12(2):121–127

    Article  PubMed  Google Scholar 

  16. Kjellman M (1996) Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res 56(18):4219–4223

    PubMed  CAS  Google Scholar 

  17. Kjellman M (1999) Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. J Clin Endocrinol Metab 84(2):730–735

    Article  PubMed  CAS  Google Scholar 

  18. Zhao J (1999) Analysis of genomic alterations in sporadic adrenocortical lesions. Gain of chromosome 17 is an early event in adrenocortical tumorigenesis. Am J Pathol 155(4):1039–1045

    PubMed  CAS  Google Scholar 

  19. Sidhu S (2002) Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab 87(7):3467–3474

    Article  PubMed  CAS  Google Scholar 

  20. Dohna M (2000) Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. Genes Chromosomes Cancer 28(2):145–152

    Article  PubMed  CAS  Google Scholar 

  21. Stephan EA (2008) Adrenocortical carcinoma survival rates correlated to genomic copy number variants. Mol Cancer Ther 7(2):425–431

    Article  PubMed  CAS  Google Scholar 

  22. Barzon L (2001) Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors. Eur J Endocrinol 145(2):207–212

    Article  PubMed  CAS  Google Scholar 

  23. Ohgaki H et al (1993) p53 mutations in sporadic adrenocortical tumors. Int J Cancer 54(3):408–410

    Article  PubMed  CAS  Google Scholar 

  24. Reincke M (1994) p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab 78(3):790–794

    Article  PubMed  CAS  Google Scholar 

  25. Reincke M (1996) p53 mutations in adrenal tumors: Caucasian patients do not show the exon 4 “hot spot” found in Taiwan. J Clin Endocrinol Metab81(10):3636–3638

    Article  PubMed  CAS  Google Scholar 

  26. Sidhu S (2005) Mutation and methylation analysis of TP53 in adrenal carcinogenesis. Eur J Surg Oncol31(5):549–554

    Article  PubMed  CAS  Google Scholar 

  27. Lin SR et al (1994) Mutations of the p53 gene in human functional adrenal neoplasms. J Clin Endocrinol Metab78(2):483–491

    Article  PubMed  CAS  Google Scholar 

  28. Gicquel C, Le Bouc Y (1997) Molecular markers for malignancy in adrenocortical tumors. Horm Res 47(4–6):269–272

    Article  PubMed  CAS  Google Scholar 

  29. Libe R (2007) Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity. Clin Cancer Res 13(3):844–850

    Article  PubMed  CAS  Google Scholar 

  30. Wachenfeld C (2001) Discerning malignancy in adrenocortical tumors: are molecular markers useful? Eur J Endocrinol 145(3):335–341

    Article  PubMed  CAS  Google Scholar 

  31. Heppner C (1999) MEN1 gene analysis in sporadic adrenocortical neoplasms. J Clin Endocrinol Metab 84(1):216–219

    Article  PubMed  CAS  Google Scholar 

  32. Gortz B (1999) MEN1 gene mutation analysis of sporadic adrenocortical lesions. Int J Cancer 80(3):373–379

    Article  PubMed  CAS  Google Scholar 

  33. Schulte KM (1999) MEN I gene mutations in sporadic adrenal adenomas. Hum Genet 105(6):603–610

    Article  PubMed  CAS  Google Scholar 

  34. Gicquel C (1994) Rearrangements at the 11p15 locus and overexpression of insulin-like growth factor-II gene in sporadic adrenocortical tumors. J Clin Endocrinol Metab 78(6):1444–1453

    Article  PubMed  CAS  Google Scholar 

  35. Gicquel C (1997) Structural and functional abnormalities at 11p15 are associated with the malignant phenotype in sporadic adrenocortical tumors: study on a series of 82 tumors. J Clin Endocrinol Metab 82(8):2559–2565

    Article  PubMed  CAS  Google Scholar 

  36. Leboulleux S (2001) Loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor 2 receptor locus: a frequent but late event in adrenocortical tumorigenesis. Eur J Endocrinol 144(2):163–168

    Article  PubMed  CAS  Google Scholar 

  37. Pilon C (1999) Inactivation of the p16 tumor suppressor gene in adrenocortical tumors. J Clin Endocrinol Metab 84(8):2776–2779

    Article  PubMed  CAS  Google Scholar 

  38. Hussussian CJ (1994) Germline p16 mutations in familial melanoma. Nat Genet 8(1):15–21

    Article  PubMed  CAS  Google Scholar 

  39. Reincke M (1993) No evidence for oncogenic mutations in guanine nucleotide-binding proteins of human adrenocortical neoplasms. J Clin Endocrinol Metab 77(5):1419–1422

    Article  PubMed  CAS  Google Scholar 

  40. Yoshimoto K (1993) Rare mutations of the Gs alpha subunit gene in human endocrine tumors. Mutation detection by polymerase chain reaction-primer-introduced restriction analysis. Cancer 72(4):1386–1393

    Article  PubMed  CAS  Google Scholar 

  41. Davies E (1997) Somatic mutations of the angiotensin II (AT1) receptor gene are not present in aldosterone-producing adenoma. J Clin Endocrinol Metab, 1997. 82(2):611–615

    Article  CAS  Google Scholar 

  42. Reincke M (1997) Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors: implications for tumorigenesis. J Clin Endocrinol Metab 82(9):3054–3058

    Article  PubMed  CAS  Google Scholar 

  43. Latronico AC (1995) No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms. J Clin Endocrinol Metab 80(3):875–877

    Article  PubMed  CAS  Google Scholar 

  44. Lin SR (1998) Alterations of RET oncogene in human adrenal tumors. Jpn J Cancer Res 89(6):634–640

    PubMed  CAS  Google Scholar 

  45. Couto JP (2009) How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer. J Clin Pathol 62(5):414–421

    Article  PubMed  CAS  Google Scholar 

  46. Sobrinho-Simoes M (2008) Intragenic mutations in thyroid cancer. Endocrinol Metab Clin North Am 37(2):333–362, viii

    Article  PubMed  CAS  Google Scholar 

  47. Karnoub AE, Weinberg RA (2008) Ras oncogenes: split personalities. Nat Rev Mol Cell Biol 9(7):517–531

    Article  PubMed  CAS  Google Scholar 

  48. DeFeo D (1981) Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A 78(6):3328–3332

    Article  PubMed  CAS  Google Scholar 

  49. Chang EH (1982) Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses. Proc Natl Acad Sci U S A 79(16):4848–4852

    Article  PubMed  CAS  Google Scholar 

  50. Hall A (1983) Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature 303(5916):396–400

    Article  PubMed  CAS  Google Scholar 

  51. Xu GF (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62(3):599–608

    Article  PubMed  CAS  Google Scholar 

  52. Kamata T, Feramisco JR (1984) Epidermal growth factor stimulates guanine nucleotide binding activity and phosphorylation of ras oncogene proteins. Nature 310(5973):147–150

    Article  PubMed  CAS  Google Scholar 

  53. Molloy CJ (1989) PDGF induction of tyrosine phosphorylation of GTPase activating protein. Nature 342(6250):711–714

    Article  PubMed  CAS  Google Scholar 

  54. Kotoula V (2009) Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas. Endocr Relat Cancer 16(2):565–572

    Article  PubMed  CAS  Google Scholar 

  55. Ameur N (2009) Mutational status of EGFR, BRAF, PI3KCA and JAK2 genes in endocrine tumors. Int J Cancer 124(3):751–753

    Article  PubMed  CAS  Google Scholar 

  56. Lin SR (1998) Mutations of K-ras oncogene in human adrenal tumours in Taiwan. Br J Cancer 77(7):1060–1065

    PubMed  CAS  Google Scholar 

  57. Yashiro T (1994) Point mutations of ras genes in human adrenal cortical tumors: absence in adrenocortical hyperplasia. World J Surg 18(4):455–60; discussion 460–461

    Article  PubMed  CAS  Google Scholar 

  58. Serrano M (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602

    Article  PubMed  CAS  Google Scholar 

  59. Benanti JA, Galloway DA (2004) Normal human fibroblasts are resistant to RAS-induced senescence. Mol Cell Biol 24(7):2842–2852

    Article  PubMed  CAS  Google Scholar 

  60. Benanti JA, Galloway DA (2004) The normal response to RAS: senescence or transformation? Cell Cycle 3(6):715–717

    PubMed  CAS  Google Scholar 

  61. Montagut C, Settleman J (2009) Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett 283(2):125–134

    Article  PubMed  CAS  Google Scholar 

  62. Davies H (2002) Mutations of the BRAF gene in human cancer. Nature417(6892):949–954

    Article  PubMed  CAS  Google Scholar 

  63. Namba H (2003) Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab88(9):4393–4397

    Article  PubMed  CAS  Google Scholar 

  64. Michaloglou C (2008) BRAF(E600) in benign and malignant human tumours. Oncogene 27(7):877–895

    Article  PubMed  CAS  Google Scholar 

  65. Michaloglou C (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436(7051):720–724

    Article  PubMed  CAS  Google Scholar 

  66. Masi G (2009) Investigation of BRAF and CTNNB1 activating mutations in adrenocortical tumors. J Endocrinol Invest 32(7):597–600

    PubMed  CAS  Google Scholar 

  67. Brose MS (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62(23):6997–7000

    PubMed  CAS  Google Scholar 

  68. Gorden A (2003) Analysis of BRAF and N-RAS mutations in metastatic melanoma tissues. Cancer Res 63(14):3955–3957

    PubMed  CAS  Google Scholar 

  69. Fassnacht, M (2003) N-terminal proopiomelanocortin acts as a mitogen in adrenocortical tumor cells and decreases adrenal steroidogenesis. J Clin Endocrinol Metab 88(5):2171–2179

    Article  PubMed  CAS  Google Scholar 

  70. Liu P (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8(8):627–644

    Article  PubMed  CAS  Google Scholar 

  71. Fassnacht M (2005) AKT is highly phosphorylated in pheochromocytomas but not in benign adrenocortical tumors. J Clin Endocrinol Metab 90(7):4366–4370

    Article  PubMed  CAS  Google Scholar 

  72. Barlaskar FM (2009) Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma. J Clin Endocrinol Metab 94(1):204–212

    Article  PubMed  CAS  Google Scholar 

  73. Sasano H (1998) Vascularity in human adrenal cortex. Mod Pathol 11(4):329–333

    PubMed  CAS  Google Scholar 

  74. Diaz-Cano SJ (2001) Contribution of the microvessel network to the clonal and kinetic profiles of adrenal cortical proliferative lesions. Hum Pathol 32(11):1232–1239

    Article  PubMed  CAS  Google Scholar 

  75. Bernini GP (2002) Angiogenesis in human normal and pathologic adrenal cortex. J Clin Endocrinol Metab 87(11):4961–4965

    Article  PubMed  CAS  Google Scholar 

  76. Giordano TJ (2009) Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res 15(2):668–676

    Article  PubMed  CAS  Google Scholar 

  77. de Fraipont F (2000) Expression of the angiogenesis markers vascular endothelial growth factor-A, thrombospondin-1, and platelet-derived endothelial cell growth factor in human sporadic adrenocortical tumors: correlation with genotypic alterations. J Clin Endocrinol Metab 85(12):4734–4741

    Article  PubMed  Google Scholar 

  78. Britvin TA (2005) Vascular endothelium growth factor in the sera of patients with adrenal tumors. Bull Exp Biol Med 140(2):228–230

    Article  PubMed  CAS  Google Scholar 

  79. Kolomecki K (2001) Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours. Endocr Regul 35(1):9–16

    PubMed  CAS  Google Scholar 

  80. Jurczynska J (2009) Peripheral blood concentrations of vascular endothelial growth factor and its soluble receptors (R1 and R2) in patients with adrenal cortex tumours treated by surgery. Endokrynol Pol 60(1):9–13

    PubMed  CAS  Google Scholar 

  81. Lacroix A (2009) Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction. Clin Endocrinol (Oxf), Aug 29 epub ahead of print

    Google Scholar 

  82. Lacroix A (2001) Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocr Rev 22(1):75–110

    Article  PubMed  CAS  Google Scholar 

  83. Louiset E (2008) Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol. Endocr Relat Cancer 15(4):1025–1034

    Article  PubMed  CAS  Google Scholar 

  84. Horvath A (2006) A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 38(7):794–800

    Article  PubMed  CAS  Google Scholar 

  85. Horvath A et al (2008) Mutation in PDE8B, a cyclic AMP-specific phosphodiesterase in adrenal hyperplasia. N Engl J Med 358(7):750–752

    Article  PubMed  CAS  Google Scholar 

  86. Kirschner LS (2000) Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 26(1):89–92

    Article  PubMed  CAS  Google Scholar 

  87. Willenberg HS (1998) Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing Cushing’s syndrome. N Engl J Med 339(1):27–31

    Article  PubMed  CAS  Google Scholar 

  88. Schteingart DE (2001) Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome. J Clin Endocrinol Metab 86(8):3968–3974

    Article  PubMed  CAS  Google Scholar 

  89. Luton JP (1990) Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 322(17):1195–1201

    Article  PubMed  CAS  Google Scholar 

  90. Icard P (2001) Adrenocortical carcinomas: surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons study group. World J Surg 25(7):891–897

    Article  PubMed  CAS  Google Scholar 

  91. Fidler WJ (1977) Ovarian thecal metaplasia in adrenal glands. Am J Clin Pathol 67(4):318–323

    PubMed  CAS  Google Scholar 

  92. Wont TW, Warner NE (1971) Ovarian thecal metaplasia in the adrenal gland. Arch Pathol 92(5):319–328

    PubMed  CAS  Google Scholar 

  93. Ulrich-Lai YM (2006) Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner. Am J Physiol Endocrinol Metab 291(5):E965–973

    Article  PubMed  CAS  Google Scholar 

  94. Else T, Hammer GD (2005) Genetic analysis of adrenal absence: agenesis and aplasia. Trends Endocrinol Metab 16(10):458–468

    Article  PubMed  CAS  Google Scholar 

  95. Zwermann O (2005) ACTH 1-24 inhibits proliferation of adrenocortical tumors in vivo. Eur J Endocrinol 153(3):435–444

    Article  PubMed  CAS  Google Scholar 

  96. Tacon LJ (2009) The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors. J Clin Endocrinol Metab 94(11):4591–4599

    Article  PubMed  CAS  Google Scholar 

  97. Gazdar AF (1990) Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis. Cancer Res 50(17):5488–5496

    PubMed  CAS  Google Scholar 

  98. Somjen D (2003) Carboxy derivatives of isoflavones as affinity carriers for cytotoxic drug targeting in adrenocortical H295R carcinoma cells. J Endocrinol 179(3):395–403

    Article  PubMed  CAS  Google Scholar 

  99. Barzon L (2008) Expression of aromatase and estrogen receptors in human adrenocortical tumors. Virchows Arch 452(2):181–191

    Article  PubMed  CAS  Google Scholar 

  100. Montanaro D (2005) Antiestrogens upregulate estrogen receptor beta expression and inhibit adrenocortical H295R cell proliferation. J Mol Endocrinol 35(2):245–256

    Article  PubMed  CAS  Google Scholar 

  101. Parker KL, Schimmer BP (1997) Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev 18(3):361–377

    Article  PubMed  CAS  Google Scholar 

  102. Luo X (1999) Steroidogenic factor 1 (SF-1) is essential for endocrine development and function. J Steroid Biochem Mol Biol 69(1–6):13–18

    Article  PubMed  CAS  Google Scholar 

  103. Beuschlein F (2002) Steroidogenic factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy. Endocrinology 143(8):3122–3135

    Article  PubMed  CAS  Google Scholar 

  104. Doghman M (2009) Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists. J Clin Endocrinol Metab 94(6):2178–2183

    Article  PubMed  CAS  Google Scholar 

  105. Doghman M (2007) Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endocrinol 21(12):2968–2987

    Article  PubMed  CAS  Google Scholar 

  106. Almeida MQ (2010) Steroidogenic factor 1 overexpression and gene amplification are more frequent in adrenocortical tumors from children than from adults. J Clin Endocrinol Metab 95(3):1458–1462

    Google Scholar 

  107. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767

    Article  PubMed  CAS  Google Scholar 

  108. Lynch HT (2009) Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet 76(1):1–18

    Article  PubMed  CAS  Google Scholar 

  109. Imai K, Yamamoto H (2008) Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29(4):673–680

    Article  PubMed  CAS  Google Scholar 

  110. Allred DC et al (2001) Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 8(1):47–61

    Article  PubMed  CAS  Google Scholar 

  111. Bevona C (2003) Cutaneous melanomas associated with nevi. Arch Dermatol 139(12):1620–1624; discussion 1624

    Article  PubMed  Google Scholar 

  112. Tadjine M (2008) Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. Clin Endocrinol (Oxf) 68(2):264–270

    CAS  Google Scholar 

  113. Tissier F (2005) Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res 65(17):7622–7627

    PubMed  CAS  Google Scholar 

  114. Soon PS (2008) Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors. Ann Surg 247(1):157–164

    Article  PubMed  Google Scholar 

  115. Gicquel C (2001) Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res 61(18):6762–6767

    PubMed  CAS  Google Scholar 

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  1. Department of Internal Medicine – Division of Metabolism, Endocrinology & Diabetes, University of Michigan Health System, University of Michigan, Domino’s Farms, Lobby C, Suite 1300, 24 Frank Lloyd Wright Drive, PO Box 451, Ann Arbor, MI, 48106, USA

    Tobias Else

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  1. Zina Pitcher Place 109, Ann Arbor, 48109-2200, Michigan, USA

    Gary D. Hammer

  2. Dept. Internal Medicine, Div. Pulmonary & Critical Care Medicine, University of Michigan Health System, Zina Pitcher Place 109, Ann Arbor, 48109-2200, Michigan, USA

    Tobias Else

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Else, T. (2009). Cellular and Molecular Pathology of Adrenocortical Carcinoma. In: Hammer, G., Else, T. (eds) Adrenocortical Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77236-3_9

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