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Immunohistochemical Biomarkers of Adrenal Cortical Neoplasms

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Abstract

Careful morphological evaluation forms the basis of the workup of an adrenal cortical neoplasm. However, the adoption of immunohistochemical biomarkers has added tremendous value to enhance diagnostic accuracy. The authors provide a brief review of immunohistochemical biomarkers that have been used in the confirmation of adrenal cortical origin and in the detection of the source of functional adrenal cortical proliferations, as well as diagnostic, predictive, and prognostic biomarkers of adrenal cortical carcinoma. In addition, a brief section on potential novel theranostic biomarkers in the prediction of treatment response to mitotane and other relevant chemotherapeutic agents is also provided. In the era of precision and personalized medical practice, adoption of combined morphology and immunohistochemistry provides a new approach to the diagnostic workup of adrenal cortical neoplasms, reflecting the evolution of clinical responsibility of pathologists.

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References

  1. Duan K, Giordano TJ, Mete O. Adrenal cortical proliferations. In: Mete O, Asa SL, eds. Endocrine Pathology. Cambridge: Cambridge University Press; 2016:602–627.

    Google Scholar 

  2. Duregon E, Volante M, Bollito E, et al. Pitfalls in the diagnosis of adrenocortical tumors: a lesson from 300 consultation cases. Hum Pathol. 2015; 46:1799–1807.

    Article  PubMed  Google Scholar 

  3. Lapinski JE, Chen L, Zhou M. Distinguishing clear cell renal cell carcinoma, retroperitoneal paraganglioma, and adrenal cortical lesions on limited biopsy material: utility of immunohistochemical markers. Appl Immunohistochem Mol Morphol. 2010; 18:414–421.

    Article  PubMed  CAS  Google Scholar 

  4. Ozisik G, Achermann JC, Meeks JJ, Jameson JL. SF1 in the development of the adrenal gland and gonads. Horm Res. 2003;59 Suppl 1:94–98.

    PubMed  CAS  Google Scholar 

  5. Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, et al. The Complementary Role of Transcription Factors in the Accurate Diagnosis of Clinically Nonfunctioning Pituitary Adenomas. Endocr Pathol. 2015; 26:349–355.

    Article  PubMed  CAS  Google Scholar 

  6. Sbiera S, Schmull S, Assie G, et al. High diagnostic and prognostic value of steroidogenic factor-1 expression in adrenal tumors. J Clin Endocrinol Metab. 2010;95: E161–E171.

    Article  PubMed  CAS  Google Scholar 

  7. Duregon E, Volante M, Giorcelli J, et al. Diagnostic and prognostic role of steroidogenic factor 1 in adrenocortical carcinoma: a validation study focusing on clinical and pathologic correlates. Hum Pathol. 2013; 44:822–828.

    Article  PubMed  CAS  Google Scholar 

  8. Busam KJ, Iversen K, Coplan KA, et al. Immunoreactivity for A103, an antibody to melan-A (Mart-1), in adrenocortical and other steroid tumors. Am J Surg Pathol. 1998; 22:57–63.

    Article  PubMed  CAS  Google Scholar 

  9. Mete O, van der Kwast TH. Epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms. Arch Pathol Lab Med. 2011; 135:665–670.

    PubMed  Google Scholar 

  10. Taskin OC, Gucer H, Mete O. An Unusual Adrenal Cortical Nodule: Composite Adrenal Cortical Adenoma and Adenomatoid Tumor. Endocr Pathol. 2015; 26:370–373.

    Article  PubMed  Google Scholar 

  11. Papotti M, Volante M, Duregon E, et al. Adrenocortical tumors with myxoid features: a distinct morphologic and phenotypical variant exhibiting malignant behavior. Am J Surg Pathol. 2010; 34:973–983.

    Article  PubMed  Google Scholar 

  12. Papathomas TG, Duregon E, Korpershoek E, et al. Sarcomatoid adrenocortical carcinoma: a comprehensive pathological, immunohistochemical, and targeted next-generation sequencing analysis. Hum Pathol. 2016; 58:113–122.

    Article  PubMed  CAS  Google Scholar 

  13. Zheng S, Cherniack AD, Dewal N, et al. Comprehensive pangenomic characterization of adrenocortical carcinoma. Cancer Cell. 2016; 29:723–736.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Duan K, Mete O. Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers. Cancer Cytopathol. 2016; 124:871–884.

    Article  PubMed  Google Scholar 

  15. Mete O, Kapran Y, Güllüoğlu MG, et al. Anti-CD10 (56C6) is expressed variably in adrenocortical tumors and cannot be used to discriminate clear cell renal cell carcinomas. Virchows Arch. 2010; 456:515–521.

    Article  PubMed  CAS  Google Scholar 

  16. Sangoi AR, Fujiwara M, West RB, et al. Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases. Am J Surg Pathol. 2011; 35:678–686.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Xia QY, Wang XT, Zhan XM, et al. Xp11 Translocation Renal Cell Carcinomas (RCCs) With RBM10-TFE3 Gene Fusion Demonstrating Melanotic Features and Overlapping Morphology With t(6;11) RCC: Interest and Diagnostic Pitfall in Detecting a Paracentric Inversion of TFE3. Am J Surg Pathol. 2017; 41:663–676.

    Article  PubMed  Google Scholar 

  18. Hayashi T, Gucer H, Mete O. A mimic of sarcomatoid adrenal cortical carcinoma: epithelioid angiosarcoma occurring in adrenal cortical adenoma. Endocr Pathol. 2014; 25:404–409.

    Article  PubMed  Google Scholar 

  19. Takizawa K, Kohashi K, Negishi T, et al. A exceptional collision tumor of primary adrenal angiosarcoma and non-functioning adrenocortical adenoma. Pathol Res Pract. 2017; 213: 702–705.

    Article  PubMed  CAS  Google Scholar 

  20. Ross JS, Wang K, Rand JV, et al. Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies. J Clin Pathol. 2014; 67:968–973.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Duan K, Gomez Hernandez K, Mete O. Clinicopathological correlates of adrenal Cushing's syndrome. J Clin Pathol. 2015; 68:175–186.

    Article  PubMed  CAS  Google Scholar 

  22. Mete O, Asa SL. Morphological distinction of cortisol-producing and aldosterone-producing adrenal cortical adenomas: not only possible but a critical clinical responsibility. Histopathology. 2012; 60:1015–1016; author reply 1016-7.

    Article  PubMed  Google Scholar 

  23. Duan K, Mete O. Clinicopathologic Correlates of Primary Aldosteronism. Arch Pathol Lab Med. 2015; 139:948–954.

    Article  PubMed  CAS  Google Scholar 

  24. Mete O, Duan K. The many faces of primary aldosteronism and Cushing syndrome: A reflection of Adrenocortical Tumour Heterogeneity. Front Med. 2018; 5:54. doi: https://doi.org/10.3389/fmed.2018.00054

    Article  Google Scholar 

  25. Funder JW, Carey RM, Mantero F, et al. Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016; 101: 1889–1916.

    Article  PubMed  CAS  Google Scholar 

  26. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004; 89: 1045–1050.

    Article  PubMed  CAS  Google Scholar 

  27. Rossi GP, Bernini G, Caliumi C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006; 48: 2293–2300.

    Article  PubMed  CAS  Google Scholar 

  28. Nanba AT, Nanba K, Byrd JB, et al. Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism. Clin Endocrinol (Oxf). 2017; 87:665–672.

    Article  PubMed  CAS  Google Scholar 

  29. Dekkers T, ter Meer M, Lenders JW, et al. (2014). Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit? J Clin Endocrinol Metab. 99: E1341-EE135.

    Article  PubMed  CAS  Google Scholar 

  30. Nakamura Y, Felizola SJ, Satoh F, Konosu-Fukaya S, Sasano H. Dissecting the molecular pathways of primary aldosteronism. Pathol. Int., 2014; 64: 482–489.

    Article  PubMed  CAS  Google Scholar 

  31. Nanba K, Chen AX, Omata K, et al. Molecular heterogeneity in aldosterone-producing adenomas. J. Clin. Endocrinol. Metab. 2016; 101: 999–1007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Seccia TM, Caroccia B, Gomez-Sanchez EP, et al. Review of Markers of Zona Glomerulosa and Aldosterone-Producing Adenoma Cells. Hypertension. 2017; 70:867–874.

    Article  PubMed  CAS  Google Scholar 

  33. Doi M, Satoh F, Maekawa T, et al. Isoform-Specific Monoclonal Antibodies Against 3-Hydroxysteroid Dehydrogenase/Isomerase Family Provide Markers for Subclassification of Human Primary Aldosteronism. J Clin EndocrinolMetab, 2014: 99; E257–E262.

    Article  CAS  Google Scholar 

  34. Gomez-Sanchez CE, Qi X, Velarde-Miranda C, et al. Development of monoclonal antibodies against human CYP11B1 and CYP11B2. Mol Cell Endocrinol. 2014;383: 111–117.

    Article  PubMed  CAS  Google Scholar 

  35. Nakamura Y, Maekawa T, Felizola S, et al. Adrenal CYP11B1/2 expression in primary aldosteronism: Immunohistochemical analysis using novel monoclonal antibodies. Moll Cell Endocrinol. 2014; 392: 73–79.

    Article  CAS  Google Scholar 

  36. Nishimoto K, Tomlins SA, Kuick R, et al. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands. Proc Natl Acad Sci U S A. 2015; 112(33): E4591–E4599.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Yamazaki Y, Nakamura Y, Omata K, et al. Histopathological classification of cross-sectional image negative hyperaldosteronism. J Clin Endocrinol Metab. 2017; 102: 1182–1192.

    PubMed  Google Scholar 

  38. Konosu-Fukaya S, Nakamura Y, Satoh F, et al. 3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma. Moll Cell Endocrinol, 2015; 408: 205–212.

    Article  CAS  Google Scholar 

  39. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989; 13:202–206.

    Article  PubMed  CAS  Google Scholar 

  40. Aubert S, Wacrenier A, Leroy X, et al. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol. 2002; 26:1612–1619.

    Article  PubMed  Google Scholar 

  41. Volante M, Bollito E, Sperone P, et al. Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification. Histopathology. 2009; 55:535–543.

    Article  PubMed  Google Scholar 

  42. Duregon E, Fassina A, Volante M, et al. The reticulin algorithm for adrenocortical tumor diagnosis: a multicentric validation study on 245 unpublished cases. Am J Surg Pathol. 2013; 37:1433–1440.

    Article  PubMed  Google Scholar 

  43. Pennanen M, Heiskanen I, Sane T, et al. Helsinki score-a novel model for prediction of metastases in adrenocortical carcinomas. Hum Pathol. 2015; 46:404–410.

    Article  PubMed  Google Scholar 

  44. Duregon E, Cappellesso R, Maffeis V, et al. Validation of the prognostic role of the “Helsinki Score” in 225 cases of adrenocortical carcinoma. Hum Pathol. 2017; 62:1–7.

    Article  PubMed  Google Scholar 

  45. Papotti M, Libè R, Duregon E, et al. The Weiss score and beyond histopathology for adrenocortical carcinoma. Horm Cancer. 2011; 2:333–340.

    Article  PubMed  CAS  Google Scholar 

  46. Bisceglia M, Ludovico O, Di Mattia A, Ben-Dor D, Sandbank J, Pasquinelli G, Lau SK, Weiss LM. Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol 2004; 12:231–243.

    Article  PubMed  Google Scholar 

  47. Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO Classification of Tumours of Endocrine Organs. 4th edn. Lyon: IARC; 2017.

    Google Scholar 

  48. Mete O, Gucer H, Kefeli M, Asa SL. Diagnostic and Prognostic Biomarkers of Adrenal Cortical Carcinoma. Am J Surg Pathol. 2018; 42:201–213.

    Article  PubMed  Google Scholar 

  49. Fonseca D, Murthy SS, Tagore KR, et al. Diagnosis of Adrenocortical Tumors by Reticulin Algorithm. Indian J Endocrinol Metab. 2017;21(5):734–737.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Else T, Kim AC, Sabolch A, et al. Adrenocortical carcinoma. Endocr Rev. 2014; 35:282–326.

    Article  PubMed  CAS  Google Scholar 

  51. Shenouda M, Brown LG, Denning KL, Pacioles T. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential. Cureus. 2016; 8: e638.

    PubMed  PubMed Central  Google Scholar 

  52. Tissier F. Classification of adrenal cortical tumors: what limits for the pathological approach? Best Pract Res Clin Endocrinol Metab. 2010; 24:877–885.

    Article  PubMed  CAS  Google Scholar 

  53. Duregon E, Volante M, Rapa I, et al. Dissecting morphological and molecular heterogeneity in adrenocortical carcinoma. Turk Patoloji Derg. 2015;31 (suppl 1):98–104.

    PubMed  Google Scholar 

  54. Mete O, Asa SL. Precursor lesions of endocrine system neoplasms. Pathology. 2013; 45:316–330.

    Article  PubMed  CAS  Google Scholar 

  55. Heaton JH, Wood MA, Kim AC, et al. Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and β-catenin. Am J Pathol. 2012; 181:1017–1033.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Giordano TJ, Kuick R, Else T, et al. Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res. 2009; 15:668–676.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. de Reyniès A, Assié G, Rickman DS, et al. Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. J Clin Oncol. 2009; 27:1108–1115.

    Article  PubMed  Google Scholar 

  58. Erickson LA, Jin L, Sebo TJ, et al. Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms. Endocr Pathol. 2001; 12:429–435.

    Article  PubMed  CAS  Google Scholar 

  59. Schmitt A, Saremaslani P, Schmid S, et al. IGFII and MIB1 immunohistochemistry is helpful for the differentiation of benign from malignant adrenocortical tumours. Histopathology. 2006;49: 298–307.

    Article  PubMed  CAS  Google Scholar 

  60. Wang C, Sun Y, Wu H, et al. Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers. Histopathology. 2014; 64:567–576.

    Article  PubMed  Google Scholar 

  61. McNicol AM, Nolan CE, Struthers AJ, et al. Expression of p53 in adrenocortical tumours: clinicopathological correlations. J Pathol. 1997; 181:146–152.

    Article  PubMed  CAS  Google Scholar 

  62. Reincke M, Karl M, Travis WH, et al. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab. 1994; 78:790–794.

    PubMed  CAS  Google Scholar 

  63. Stojadinovic A, Brennan MF, Hoos A, et al. Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis. Mod Pathol. 2003; 16:742–751.

    Article  PubMed  Google Scholar 

  64. Das S, Sengupta M, Islam N, et al. Weineke criteria, Ki-67 index and p53 status to study pediatric adrenocortical tumors: is there a correlation? J Pediatr Surg. 2016; 51:1795–1800.

    Article  PubMed  Google Scholar 

  65. Stojadinovic A, Ghossein RA, Hoos A, et al. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol. 2002; 20:941–950.

    Article  PubMed  CAS  Google Scholar 

  66. Edgren M, Eriksson B, Wilander E, et al. Biological characteristics of adrenocortical carcinoma: a study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas. Anticancer Res. 1997; 17:1303–1309.

    PubMed  CAS  Google Scholar 

  67. Arola J, Salmenkivi K, Liu J, et al. p53 and Ki67 in adrenocortical tumors. Endocr Res. 2000; 26:861–865.

    Article  PubMed  CAS  Google Scholar 

  68. Morimoto R, Satoh F, Murakami O, et al. Immunohistochemistry of a proliferation marker Ki67/MIB1 in adrenocortical carcinomas: Ki67/MIB1 labeling index is a predictor for recurrence of adrenocortical carcinomas. Endocr J. 2008; 55:49–55.

    Article  PubMed  Google Scholar 

  69. Pereira SS, Morais T, Costa MM, Monteiro MP, Pignatelli D. The emerging role of the molecular marker p27 in the differential diagnosis of adrenocortical tumors. Endocr Connect. 2013; 2:137–145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Han VK, Lu F, Bassett N, et al. Insulin-like growth factor-II (IGF-II) messenger ribonucleic acid is expressed in steroidogenic cells of the developing ovine adrenal gland: evidence of an autocrine/paracrine role for IGF-II. Endocrinology. 1992; 131:3100–3109.

    Article  PubMed  CAS  Google Scholar 

  71. Nielsen HM, How-Kit A, Guerin C, et al. Copy number variations alter methylation and parallel IGF2 overexpression in adrenal tumors. Endocr Relat Cancer. 2015; 22:953–967.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Boulle N, Logié A, Gicquel C, et al. Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. J Clin Endocrinol Metab. 1998; 83:1713–1720.

    PubMed  CAS  Google Scholar 

  73. Boulle N, Gicquel C, Logie A, et al. Fibroblast growth factor-2 inhibits the maturation of pro-insulin-like growth factor-II (Pro-IGF-II) and the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in the human adrenocortical tumor cell line NCI-H295R. Endocrinology. 2000; 141:3127–3136.

    Article  PubMed  CAS  Google Scholar 

  74. Pinto EM, Chen X, Easton J, et al. Genomic landscape of paediatric adrenocortical tumours. Nat Commun. 2015; 6:6302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Tissier F, Cavard C, Groussin L, et al. 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. 2005; 65:7622–7627.

    Article  PubMed  CAS  Google Scholar 

  76. Åkerström T, Maharjan R, Sven Willenberg H, et al. Activating mutations in CTNNB1 in aldosterone producing adenomas. Sci Rep. 2016; 6:19546.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Assie G, Giordano TJ, Bertherat J. Gene expression profiling in adrenocortical neoplasia. Mol Cell Endocrinol. 2012; 351:111–117.

    Article  PubMed  CAS  Google Scholar 

  78. Duregon E, Molinaro L, Volante M, et al. Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma. Mod Pathol. 2014; 27:1246–1254.

    Article  PubMed  CAS  Google Scholar 

  79. Giordano TJ. The argument for mitotic rate-based grading for the prognostication of adrenocortical carcinoma. Am J Surg Pathol. 2011;35: 471–473.

    Article  PubMed  Google Scholar 

  80. Mouat IC, Giordano TJ. Assessing Biological Aggression in Adrenocortical Neoplasia. Surg Pathol Clin. 2014; 7:533–541.

    Article  PubMed  Google Scholar 

  81. Beuschlein F, Weigel J, Saeger W, et al. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab. 2015; 100:841–849.

    Article  PubMed  CAS  Google Scholar 

  82. Sasano H, Satoh F, Nakamura Y. Roles of the pathologist in evaluating surrogate markers for medical therapy in adrenocortical carcinoma. Endocr Pathol 2014; 25:366–370.

    Article  PubMed  CAS  Google Scholar 

  83. Stigliano A, Chiodini I, Giordano R, et al. Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE). J Endocrinol Invest. 2016 Jan;39(1):103–121.

    Article  PubMed  CAS  Google Scholar 

  84. Papathomas TG, Pucci E, Giordano TJ, et al. An International Ki67 Reproducibility Study in Adrenal Cortical Carcinoma. Am J Surg Pathol. 2016; 40:569–576.

    Article  PubMed  Google Scholar 

  85. Lu H, Papathomas TG, van Zessen D, et al. Automated Selection of Hotspots (ASH): enhanced automated segmentation and adaptive step finding for Ki67 hotspot detection in adrenal cortical cancer. Diagn Pathol. 2014;9: 216.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Logarinho E, Bousbaa H. Kinetochore-microtubule interactions “in check” by Bub1, Bub3 and BubR1: the dual task of attaching and signalling. Cell Cycle. 2008; 7:1763–1768.

    Article  PubMed  CAS  Google Scholar 

  87. Song L, Craney A, Rape M. Microtubule-dependent regulation of mitotic protein degradation. Mol Cell. 2014; 53:179–192.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Wrighton KH. Mitosis: microtubules protect spindle assembly factors. Nat Rev Mol Cell Biol. 2014; 15:150–151.

    Article  PubMed  CAS  Google Scholar 

  89. Fry AM. The Nek2 protein kinase: a novel regulator of centrosome structure. Oncogene. 2002; 21:6184–6194.

    Article  PubMed  CAS  Google Scholar 

  90. Fletcher L, Cerniglia GJ, Nigg EA, et al. Inhibition of centrosome separation after DNA damage: a role for Nek2. Radiat Res. 2004; 162:128–135.

    Article  PubMed  CAS  Google Scholar 

  91. Duan K, Mete O. Familial endocrine tumor syndromes: Clinical and predictive roles of molecular histopathology. AJSP: Reviews and Reports. 2017; 22:246–268.

    Google Scholar 

  92. Raymond VM, Everett JN, Furtado LV, et al. Adrenocortical carcinoma is a lynch syndrome-associated cancer. J Clin Oncol. 2013; 31:3012–3018.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Else T, Lerario AM, Everett J, et al. Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series. Eur J Endocrinol. 2017; 177:439–444.

    Article  PubMed  Google Scholar 

  94. Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7; 366(:2189–2197.

  95. Creemers SG, Hofland LJ, Korpershoek E, et al. Future directions in the diagnosis and medical treatment of adrenocortical carcinoma. Endocr Relat Cancer. 2016; 23: R43–R69.

    Article  PubMed  CAS  Google Scholar 

  96. Scheidt HA, Haralampiev I, Theisgen S, et al. The adrenal specific toxicant mitotane directly interacts with lipid membranes and alters membrane properties depending on lipid composition. Mol Cell Endocrinol. 2016; 428:68–81.

    Article  PubMed  CAS  Google Scholar 

  97. Kroiss M, Plonné D, Kendl S, et al. Association of mitotane with chylomicrons and serum lipoproteins: practical implications for treatment of adrenocortical carcinoma. Eur J Endocrinol. 2016; 174:343–353.

    Article  PubMed  CAS  Google Scholar 

  98. Ronchi CL, Sbiera S, Volante M, et al. CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma. PLoS One. 2014; 9: e105855.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Volante M, Terzolo M, Fassnacht M, et al. Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer. Clin Cancer Res. 2012; 18:3452–3461.

    Article  PubMed  CAS  Google Scholar 

  100. Jordheim LP, Sève P, Trédan O, Dumontet C. The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. Lancet Oncol. 2011; 12:693–702.

    Article  PubMed  CAS  Google Scholar 

  101. Germano A, Rapa I, Volante M, et al. RRM1 modulates mitotane activity in adrenal cancer cells interfering with its metabolization. Mol Cell Endocrinol. 2015; 401:105–110.

    Article  PubMed  CAS  Google Scholar 

  102. Barsanti-Innes B, Hey SP, Kimmelman J. The Challenges of Validating in Precision Medicine: The Case of Excision Repair Cross-Complement Group 1 Diagnostic Testing. Oncologist. 2017; 22:89–96.

    Article  PubMed  Google Scholar 

  103. Laufs V, Altieri B, Sbiera S, et al. ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas. Eur J Endocrinol. 2017 Nov 29. pii: EJE-17-0788. doi: https://doi.org/10.1530/EJE-17-0788.

  104. Roca E, Berruti A, Sbiera S, et al. Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer. Endocr Relat Cancer. 2017; 24:299–307.

    Article  PubMed  Google Scholar 

  105. Henning JEK, Deutschbein T, Altieri B, et al. Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors. J Clin Endocrinol Metab. 2017; 102:4323–4332.

    Article  PubMed  Google Scholar 

  106. Ruggiero C, Doghman-Bouguerra M, Sbiera S, et al. Dosage-dependent regulation of VAV2 expression by steroidogenic factor-1 drives adrenocortical carcinoma cell invasion. Sci Signal. 2017;10(469).

  107. Sbiera S, Sbiera I, Ruggiero C, et al. Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2017; 102:3491–3498.

    Article  PubMed  Google Scholar 

  108. Ruggiero C, Lalli E. VAV2: a novel prognostic marker and a druggable target for adrenocortical carcinoma. Oncotarget. 2017; 8:88257–88258.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Celso E. Gomez-Sanchez for providing the CYP11B1/2 monoclonal antibody for immunohistochemistry and Dr. Masao Doi and Dr. Hitoshi Okamura for providing the HSD3B1/2 monoclonal antibody.

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Authors and Affiliations

  1. Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, ON, M5G 2C4, Canada

    Ozgur Mete & Sylvia L. Asa

  2. Departments of Pathology and Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA

    Thomas J. Giordano

  3. Department of Pathology, Turin University at Molinette Hospital, Turin, Italy

    Mauro Papotti

  4. Department of Pathology, Tohoku University School of Medicine, Sendai, Japan

    Hironobu Sasano

  5. Department of Oncology, University of Turin at San Luigi Hospital, Turin University, Orbassano, Turin, Italy

    Marco Volante

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  1. Ozgur Mete
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Correspondence to Ozgur Mete.

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Mete, O., Asa, S.L., Giordano, T.J. et al. Immunohistochemical Biomarkers of Adrenal Cortical Neoplasms. Endocr Pathol 29, 137–149 (2018). https://doi.org/10.1007/s12022-018-9525-8

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