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Endocrine Tumors of the Gastrointestinal System

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Abstract

Endocrine tumors of the gastrointestinal tract constitute a heterogeneous anatomical and functional group of cells with respect to clinical syndromes, clinico-pathological associations, and prognosis. The WHO classification is now used for the diagnosis and classification of these tumors with respect to anatomical location, tumor cell type, and differentiation. These include well-differentiated endocrine tumors with benign behavior, low-grade well-differentiated endocrine carcinomas, and high-grade poorly differentiated endocrine carcinomas. Cellular and molecular studies, such as Ki67 index, p53 overexpression or mutations, and loss of heterozygosity have contributed to the understanding of these tumors and the ability to predict the behavior of these tumors.

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References

  1. Heidenhain R (1870) Unterschunger über den Bau der Labdrüser. Ark Mikrosk Anat 6:368–406

    Google Scholar 

  2. Nicolas A (1891) Recherches sur l'épithélium de l'intestine grele. Int Mschr Anat Physiol 8:1–8

    Google Scholar 

  3. Kultschitzky N (1897) Zur Frage über den Bau des Darmcanals. Arch Mikrosk Anat 49:7–35

    Google Scholar 

  4. Schmidt JE (1905) Beiträge zur normalen und patologischen Histologie eininger Zellarten der Schleimhaut des menschlichen Darm-Kanals. Arch Mikrosk Anat 66:12–40

    Google Scholar 

  5. Ciaccio C (1907) Sopra speciali cellule granulose della mucosa intestinale. Arch Ital Anat Embriol 6:482

    Google Scholar 

  6. Bayliss WM, Starling EH (1902) The mechanism of pancreatic secretion. J Physiol 28:325–353

    CAS  PubMed  Google Scholar 

  7. Bayliss WM, Starling EH (1902) On the causation of the so-called peripheral reflex secretion of the pancreas. Proc R Soc Lond B Biol Sci 69:352–353

    CAS  Google Scholar 

  8. Feyrter F (1938) Über diffuse endokrine epitheliale Organe. Liepzig Zentr Inn Mediz 29:545–571

    Google Scholar 

  9. Masson P (1914) La glande endocrine del'intestin chez l'homme. Compt Rend Hebdom Seances Acad Sci 158:52–61

    Google Scholar 

  10. Feyrter F (1953) Über die peripheren endockrinen (parakrinen) Druesen des Menschen. Maudrich W, Wien, Düsseldorf

    Google Scholar 

  11. Pearse AGE (1966) Common cytochemical properties of cells producing polypeptide hormones, with particular reference to calcitonin and C-cells. Vet Records 79:303–313

    Google Scholar 

  12. Pearse AGE (1969) The cytochemistry and ultrastructure of polypeptide-hormone producing cells of the APUD series and the embryologic, physiologic and pathologic implication of the concept. J Histochem Cytochem 17:303–313

    CAS  PubMed  Google Scholar 

  13. Erspamer V, Asero B (1952) Identification of enteramine, the specific hormone of the enetrochromaffin cell system, as 5-hydroxytryptamine. Nature 169:800–801

    CAS  PubMed  Google Scholar 

  14. Öberendorfer S (1907) Karzinoide tumoren des Dünndarms. Frankf Z Pathol 1:426–432

    Google Scholar 

  15. Gosset A, Masson P (1914) Tumeurs endcorine de l'appendice. Presse Med 25:237

    Google Scholar 

  16. Masson P (1928) Carcinoid (argentaffin-cell tumors) and nerve hyperplasia of the appendicular mucosa. Am J Pathol 4:181–212

    CAS  PubMed  Google Scholar 

  17. Rehfeld JF (1998) The new biology of gastrointestinal hormones. Physiol Rev 78:1087–1108

    CAS  PubMed  Google Scholar 

  18. Solcia E, Capella C, Fiocca R, Sessa F, LaRosa S, Rindi G (1998) Disorders of the endocrine system. In: Ming SC Goldman H (ed) Pathology of the gastrointestinal tract, 2nd edn. Williams and Wilkins, Philadelphia, pp 295–322

    Google Scholar 

  19. Bishop AE, Power RF, Polak JM (1988) Markers for neuroendocrine differentiation. Pathol Res Pract 183:119–128

    CAS  PubMed  Google Scholar 

  20. Hamperl H (1927) Über de gelben (chromaffinen) Zellen im gesunden und karnaken Magendarmschlauch. Virchows Arch 266:509–548

    Google Scholar 

  21. Grimelius L (1968) A silver nitrate stain for a2 cells in human pancreatic islets. Acta Soc Med Upsal 73:243–270

    CAS  PubMed  Google Scholar 

  22. Portela-Gomes GM (1982) Enterochromaffin cells. A qualitative and quantitative study. Acta Univ Ups 434:1–44

    Google Scholar 

  23. Bishop AE, Polak JM, Facer P, Ferri GL, Marangos PJ, pearse AG (1982) Neuron specific enolase: a common marker for the endocrine cells and innervation of the gut and pancreas. Gastroenterology 83:902–915

    Google Scholar 

  24. Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J (1983) PGP9.5 a new marker for vertebrate neurons and neuroendocrine differentiation. Brain Res 278:224–228

    Google Scholar 

  25. Rode J, Dhillon AP, Doran JF, Jackson P, Thompson RJ (1985) PGP 9.5, a new marker for human neuroendocrine tumours. Histopathology 9:147–158

    Google Scholar 

  26. Wilkinson KD, Lee KM, Desphande S, Duerksen-Hughes P, Boss JM, Pohl J (1989) The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246:670–673

    Google Scholar 

  27. Lloyd RV, Wilson BS (1983) Specific endocrine tissue marker defined by a monoclonal antibody. Science 222:628–630

    CAS  PubMed  Google Scholar 

  28. Rindi G, Buffa R, Sessa F, Tortora O, Solcia E (1986) Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules. Histochemistry 85:19–28

    Google Scholar 

  29. Suzuki H, Christofides ND, Chretien M, Seidah N, Polak JM, Bloom SR (1987) Developmental changes in immunoreactive content of novel pituitary protein 7B2 in human pancreas and its identification in pancreatic tumours. Diabetes 36:1276–1279

    CAS  PubMed  Google Scholar 

  30. Azzoni C, Yu JY, Baggi MT et al (1992) Studies on co-localization of 7B2 and pancreatic hormones in normal and tumoural islet cells. Virchows Arch A Pathol Anat Histopathol 421:457–466

    CAS  PubMed  Google Scholar 

  31. Jahn R, Schiebler W, Ouimet C, Greengard P (1985) A 38,000-dalton membrane protein (p38) present in synaptic vesicles. Proc Natl Acad Sci U S A 82:4137–4141

    CAS  PubMed  Google Scholar 

  32. Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE (1986) Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci U S A 83:3500–3504

    CAS  PubMed  Google Scholar 

  33. Buffa R, Rindi G, Sessa F et al (1988) Synaptophysin immunoreactivity and small clear vescicles in neuroendocrine cells and related tumours. Mol Cell Probes 1:367–381

    Google Scholar 

  34. Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E (1996) Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A 93:5166–5171

    CAS  PubMed  Google Scholar 

  35. Dimaline RN, Struthers J (1996) Expression and regulation of a vescicular monoamine transporter (VMAT2) in rat stomach: a putative histamine transporter. J Physiol 490:249–256

    CAS  PubMed  Google Scholar 

  36. Kolby L, Wangberg B, Ahlman H et al (1998) Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors. Digestion 59:160–166

    CAS  PubMed  Google Scholar 

  37. Rindi G, Paolotti D, Fiocca R, Wiedenmann B, Henry JP, Solcia E (2000) Vesicular monoamine transporter 2 as a marker of gastric enterochromaffin-like cell tumors. Virchows Arch 436:217–223

    CAS  PubMed  Google Scholar 

  38. Rindi G, Licini L, Necchi V et al (2007) Peptide products of the neurotrophin-inducible gene vgf are produced in human neuroendocrine cells from early development and increase in hyperplasia and neoplasia. J Clin Endocrinol Metab 92:2811–2815

    CAS  PubMed  Google Scholar 

  39. Bordi C, D’Adda T, Azzoni C, Canavese G, Brandi ML (1998) Gastointestinal endocrine tumors: recent developments. Endocr Pathol 9:99–115

    Google Scholar 

  40. Roberts WC, Sjoerdsma A (1964) The cardiac disease associated with carcinoid syndrome (carcinoid heart disease). Am J Med 36:5–34

    CAS  PubMed  Google Scholar 

  41. Reubi JC, Schaer JC, Markwalder R, Waser B, Horisberger U, Laissue J (1997) Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance. Yale J Biol Med 70:471–479

    CAS  PubMed  Google Scholar 

  42. Reubi JC, Kappeler A, Waser B, Schonbrunn A, Laissue J (1998) Immunohistochemical localization of somatostatin receptor sst2A in human pancreatic islets. Clin Endocrinol Metab 83:3746–3749

    CAS  Google Scholar 

  43. Janson ET, Stridsberg M, Gobl A, Westlin JE, Oberg K (1998) Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies. Cancer Res 58:2375–2378

    CAS  PubMed  Google Scholar 

  44. Reubi JC, Kappeler A, Waser B, Laissue J, Hipkin RW, Schonbrunn A (1998) Immunohistochemical localization of somatostatin receptors sst2A in human tumors. Am J Pathol 153:233–245

    CAS  PubMed  Google Scholar 

  45. Kulaksiz H, Eissele R, Rossler D et al (2002) Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. Gut 50:52–60

    CAS  PubMed  Google Scholar 

  46. Krenning EP, de Jong M, Kooij PPM et al (1999) Radiolabeled somatostatin analogues for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol 10:S23–S29

    PubMed  Google Scholar 

  47. Öberg K (2001) Established clinical use of octreotide and lanreotide in oncology. Chemotherapy 47(S2):40–53

    Google Scholar 

  48. Volante M, Brizzi MP, Faggiano A et al (2007) Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 20:1172–1182

    CAS  PubMed  Google Scholar 

  49. Lemmer K, Ahnert-Hilger G, Hopfner M et al (2002) Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells. Life Sci 71:667–678

    CAS  PubMed  Google Scholar 

  50. O’Toole D, Saveanu A, Couvelard A et al (2006) The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies. Eur J Endocrinol 155:849–857

    PubMed  Google Scholar 

  51. Pivonello R, Ferone D, de Herder WW et al (2004) Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors. J Clin Endocrinol Metab 89:4493–4502

    CAS  PubMed  Google Scholar 

  52. Pivonello R, Ferone D, de Herder WW et al (2004) Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metab 89:2452–2462

    CAS  PubMed  Google Scholar 

  53. Pivonello R, Matrone C, Filippella M et al (2004) Dopamine receptor expression and function in clinically nonfunctioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. J Clin Endocrinol Metab 89:1674–1683

    CAS  PubMed  Google Scholar 

  54. Ferone D, Arvigo M, Semino C et al (2005) Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation. Am J Physiol 289:E1044–E1050

    CAS  Google Scholar 

  55. Ferone D, Saveanu A, Culler MD et al (2007) Novel chimeric somatostatin analogs: facts and perspectives. Eur J Endocrinol 156(Suppl 1):S23–S28

    CAS  PubMed  Google Scholar 

  56. Resmini E, Dadati P, Ravetti JL et al (2007) Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab 92:1592–1599

    CAS  PubMed  Google Scholar 

  57. Hanahan D (1985) Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 315:115–122

    CAS  PubMed  Google Scholar 

  58. Rindi G, Grant SG, Yiangou Y et al (1990) Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression. Am J Pathol 136:1349–1363

    CAS  PubMed  Google Scholar 

  59. Rindi G, Efrat S, Ghatei MA, Bloom SR, Solcia E, Polak JM (1991) Glucagonomas of transgenic mice express a wide range of general neuroendocrine markers and bioactive peptides. Virchows Arch A Pathol Anat Histopathol 419:115–129

    CAS  PubMed  Google Scholar 

  60. Crabtree JS, Scacheri PC, Ward JM et al (2001) A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc Natl Acad Sci U S A 98:1118–1123

    CAS  PubMed  Google Scholar 

  61. Bertolino P, Tong WM, Galendo D, Wang ZQ, Zhang CX (2003) Heterozygous MEN1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1. Mol endocrinol 17:1880–1892

    Google Scholar 

  62. Pellegata NS, Quintanilla-Martinez L, Siggelkow H et al (2006) Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A 103:15558–15563

    CAS  PubMed  Google Scholar 

  63. Rindi G, Solcia E (2007) Endocrine hyperplasia and dysplasia in the pathogenesis of gastrointestinal and pancreatic endocrine tumors. Gastroenterol Clin North Am 36:851–865, vi

    Google Scholar 

  64. Rindi G, Villanacci V, Ubiali A, Scarpa A (2001) Endocrine tumors of the digestive tract and pancreas: histogenesis, diagnosis and molecular basis. Expert Rev Mol Diagn 1:323–333

    CAS  PubMed  Google Scholar 

  65. Brandi ML, Bordi C, Tonelli F, Falchetti A, Marx SJ (2002) Multiple endocrine neoplasia type 1. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology, 2nd edn. Academic, San Diego, pp 783–797

    Google Scholar 

  66. Larsson K, Skogseid B, Öberg K, Nakamura Y, Nordenskjöld M (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332:85–87

    CAS  PubMed  Google Scholar 

  67. Chandrasekharappa SC, Guru SC, Manickam P et al (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276:404–407

    CAS  PubMed  Google Scholar 

  68. Agarwal SK, Guru SC, Heppner C et al (1999) Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 96:143–152

    CAS  PubMed  Google Scholar 

  69. Heppner C, Bilimoria KY, Agarwal SK et al (2001) The tumor suppressor protein menin interacts with NF-κB proteins and inhibits NF-κB-mediated transactivation. Oncogene 20:4917–4925

    CAS  PubMed  Google Scholar 

  70. Beckers A, Abs R, Reyniers E et al (1994) Variable regions of chromosome 11 loss in different pathological tissues of a patient with the multiple endocrine neoplasia type I syndrome. J Clin Endocrinol Metab 79:1498–1502

    CAS  PubMed  Google Scholar 

  71. Jakobovitz O, Nass D, DeMarco L et al (1996) Carcinoid tumors frequently display genetic abnormalities involving chromosome 11. J Clin Endocrinol Metab 81:3164–3167

    CAS  PubMed  Google Scholar 

  72. Bordi C, Falchetti A, Azzoni C et al (1997) Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I. Am J Surg Pathol 21:1075–1082

    CAS  PubMed  Google Scholar 

  73. Debelenko LV, Emmert-Buck MR, Zhuang Z et al (1997) The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology 113:773–781

    CAS  PubMed  Google Scholar 

  74. D’Adda T, Keller G, Bordi C, Hofler H (1999) Loss of heterozygosity in 11q13–14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. Lab Invest 79:671–677

    PubMed  Google Scholar 

  75. Lubensky IA, Debelenko LV, Zhuang Z et al (1996) Allelic deletions on chromosome 11q13 in multiple tumors from individual MEN1 patients. Cancer Res 56:5272–5278

    CAS  PubMed  Google Scholar 

  76. Debelenko LV, Zhuang Z, Emmert-Buck MR et al (1997) Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic ­endocrine tumors. Cancer Res 57:2238–2243

    CAS  PubMed  Google Scholar 

  77. Zhuang Z, Vortmeyer AO, Pack S et al (1997) Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Res 57:4682–4686

    CAS  PubMed  Google Scholar 

  78. Mailman MD, Muscarella P, Schirmer WJ, Ellison EC, O’Dorisio TM, Prior TW (1999) Identification of MEN1 mutations in sporadic enteropancreatic neuroendocrine tumors by analysis of paraffin-embedded tissue. Clin Chem 45:29–34

    CAS  PubMed  Google Scholar 

  79. Fujii T, Kawai T, Saito K et al (1999) MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation. Pathol Int 49:968–973

    CAS  PubMed  Google Scholar 

  80. D’Adda T, Pizzi S, Azzoni C et al (2002) Different patterns of 11q allelic losses in digestive endocrine tumors. Hum Pathol 33:322–329

    PubMed  Google Scholar 

  81. Toliat MR, Berger W, Ropers HH, Neuhaus P, Wiedenmann B (1997) Mutations in the MEN I gene in sporadic neuroendocrine tumours of gastroenteropancreatic system. Lancet 350:1223

    CAS  PubMed  Google Scholar 

  82. Goebel SU, Heppner C, Burns AL et al (2000) Genotype/phenotype correlation of multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas. J Clin Endocrinol Metab 85:116–123

    CAS  PubMed  Google Scholar 

  83. Görtz B, Roth J, Krahenmann A et al (1999) Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol 154:429–436

    PubMed  Google Scholar 

  84. Higham AD, Bishop LA, Dimaline R et al (1999) Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia. Gastroenterology 116:1310–1318

    CAS  PubMed  Google Scholar 

  85. Liu L, Broaddus RR, Yao JC et al (2005) Epigenetic alterations in neuroendocrine tumors: methylation of RAS-association domain family 1, isoform A and p16 genes are associated with metastasis. Mod Pathol 18:1632–1640

    CAS  PubMed  Google Scholar 

  86. Pizzi S, Azzoni C, Bassi D, Bottarelli L, Milione M, Bordi C (2003) Genetic alterations in poorly differentiated endocrine carcinomas of the gastrointestinal tract. Cancer 98:1273–1282

    CAS  PubMed  Google Scholar 

  87. Pizzi S, Azzoni C, Bottarelli L et al (2005) RASSF1A promoter methylation and 3p21.3 loss of heterozygosity are features of foregut, but not midgut and hindgut, malignant endocrine tumours. J Pathol 206:409–416

    Google Scholar 

  88. Serrano J, Goebel SU, Peghini PL, Lubensky IA, Gibril F, Jensen RT (2000) Alterations in the p16INK4a/CDKN2A tumor suppressor gene in gastrinomas. J Clin Endocrinol Metab 85:4146–4156

    CAS  PubMed  Google Scholar 

  89. Lubomierski N, Kersting M, Bert T et al (2001) Tumor suppresor genes in the 9p21 gene cluster are selective targets of inactivation in neuroendocrine gastroenteropancreatic tumors. Cancer Res 61:5905–5910

    Google Scholar 

  90. Lohmann DR, Fesseler B, Putz B et al (1993) Infrequent mutations of the p53 gene in pulmonary carcinoid tumors. Cancer Res 53:5797–5801

    CAS  PubMed  Google Scholar 

  91. Vortmeyer AO, Lubensky IA, Merino MJ et al (1997) Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. J Natl Cancer Inst 89:1448–1453

    CAS  PubMed  Google Scholar 

  92. Rindi G, Alberizzi P, Candusso M, LaRosa S, Capella C, Solcia E (1999) Loss of heterozygosity for chromosome 17p, P53 gene, and chromosome 18q, DCC gene, in aggressive endocrine tumors of the stomach. Gastroenterology 116:G2156 (abstract)

    Google Scholar 

  93. Rindi G, Azzoni C, La Rosa S et al (1999) ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology 116:532–542

    CAS  PubMed  Google Scholar 

  94. Furlan D, Bernasconi B, Uccella S, Cerutti R, Carnevali I, Capella C (2005) Allelotypes and fluorescence in situ hybridization ­profiles of poorly differentiated endocrine carcinomas of different sites. Clin Cancer Res 11:1765–1775

    CAS  PubMed  Google Scholar 

  95. Terris B, Meddeb M, Marchio A et al (1998) Comparative genomic hybridization analysis of sporadic neuroendocrine tumors of the digestive system. Genes Chromosomes Cancer 22:50–56

    CAS  PubMed  Google Scholar 

  96. Zhao J, de Krijger RR, Meier D et al (2000) Genomic alterations in well-differentiated gastrointestinal and bronchial neuroendocrine tumors (Carcinoids): marked differences indicating diversity in molecular pathogenesis [In Process Citation]. Am J Pathol 157:1431–1438

    CAS  PubMed  Google Scholar 

  97. Kytola S, Hoog A, Nord B et al (2001) Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. Am J Pathol 158:1803–1808

    CAS  PubMed  Google Scholar 

  98. Tonnies H, Toliat MR, Ramel C et al (2001) Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by comparative genomic hybridisation. Gut 48:536–541

    CAS  PubMed  Google Scholar 

  99. Lollgen RM, Hessman O, Szabo E, Westin G, Akerstrom G (2001) Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer 92:812–815

    CAS  PubMed  Google Scholar 

  100. Petzmann S, Ullmann R, Halbwedl I, Popper HH (2004) Analysis of chromosome-11 aberrations in pulmonary and gastrointestinal carcinoids: an array comparative genomic hybridization-based study. Virchows Arch 445:151–159

    CAS  PubMed  Google Scholar 

  101. Wang GG, Yao JC, Worah S et al (2005) Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors. Mod Pathol 18:1079–1087

    CAS  PubMed  Google Scholar 

  102. Kim do H, Nagano Y, Choi IS, White JA, Yao JC, Rashid A (2008) Allelic alterations in well-differentiated neuroendocrine tumors (carcinoid tumors) identified by genome-wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors. Genes Chromosomes Cancer 47:84–92

    Google Scholar 

  103. Kulke MH, Freed E, Chiang DY et al (2008) High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer 47:591–603

    CAS  PubMed  Google Scholar 

  104. Pizzi S, D’Adda T, Azzoni C et al (2002) Malignancy-associated allelic losses on the X-chromosome in foregut but not in midgut endocrine tumours. J Pathol 196:401–407

    PubMed  Google Scholar 

  105. Missiaglia E, Moore PS, Williamson J et al (2002) Sex chromosome anomalies in pancreatic endocrine tumors. Int J Cancer 98:532–538

    CAS  PubMed  Google Scholar 

  106. D’Adda T, Bottarelli L, Azzoni C et al (2005) Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. Mod Pathol 18:795–805

    PubMed  Google Scholar 

  107. Azzoni C, Bottarelli L, Pizzi S, D’Adda T, Rindi G, Bordi C (2006) Xq25 and Xq26 identify the common minimal deletion region in malignant gastroenteropancreatic endocrine carcinomas. Virchows Arch 448:119–126

    PubMed  Google Scholar 

  108. Gerdes B, Ramaswamy A, Simon B et al (1999) Analysis of beta-catenin gene mutations in pancreatic tumors. Digestion 60:544–548

    CAS  PubMed  Google Scholar 

  109. Semba S, Kusumi R, Moriya T, Sasano H (2000) Nuclear accumulation of B-catenin in human endocrine tumors: association with Ki-67 (MIB-1) proliferative activity. Endocr Pathol 11:243–250

    CAS  PubMed  Google Scholar 

  110. Fujimori M, Ikeda S, Shimizu Y, Okajima M, Asahara T (2001) Accumulation of beta-catenin protein and mutations in exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor. Cancer Res 61:6656–6659

    CAS  PubMed  Google Scholar 

  111. Barshack I, Goldberg I, Chowers Y, Horowitz A, Kopolovic J (2002) Different beta-catenin immunoexpression in carcinoid tumors of the appendix in comparison to other gastrointestinal carcinoid tumors. Pathol Res Pract 198:531–536

    PubMed  Google Scholar 

  112. Li CC, Xu B, Hirokawa M et al (2002) Alterations of E-cadherin, alpha-catenin and beta-catenin expression in neuroendocrine tumors of the gastrointestinal tract. Virchows Arch 440: 145–154

    CAS  PubMed  Google Scholar 

  113. Hervieu V, Lepinasse F, Gouysse G et al (2006) Expression of beta-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases. J Clin Pathol 59:1300–1304

    CAS  PubMed  Google Scholar 

  114. Su MC, Wang CC, Chen CC et al (2006) Nuclear translocation of beta-catenin protein but absence of beta-catenin and APC mutation in gastrointestinal carcinoid tumor. Ann Surg Oncol 13:1604–1609

    PubMed  Google Scholar 

  115. Pizzi S, Azzoni C, Tamburini E et al (2008) APC alteration in digestive endocrine tumours: correlation with nuclear translocation of {beta}-catenin and chromosomal instability. Endocrine-related cancer 15(4):1013–1024

    Google Scholar 

  116. Nakakura EK, Sriuranpong VR, Kunnimalaiyaan M et al (2005) Regulation of neuroendocrine differentiation in gastrointestinal carcinoid tumor cells by notch signaling. J Clin Endocrinol Metab 90:4350–4356

    CAS  PubMed  Google Scholar 

  117. Solcia E, Klöppel G, Sobin LH (2000) Histological typing of endocrine tumours, 2nd edn. Springer-Verlag, New York

    Google Scholar 

  118. Soga J, Tazawa K (1971) Pathologic analysis of carcinoids; histologic reevaluation of 62 cases. Cancer 28:990–998

    CAS  PubMed  Google Scholar 

  119. Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E (1993) Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study [see comments]. Gastroenterology 104:994–1006

    CAS  PubMed  Google Scholar 

  120. Kim T, Tao-Cheng J-H, Eiden LE, Loh PY (2001) Chromogranin A, an “On/Off” switch controlling dense-core secretory granule biogenesis. Cell 106:499–509

    Google Scholar 

  121. Rigaud G, Missiaglia E, Moore PS et al (2001) High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications. Cancer Res 61(1):285–292

    Google Scholar 

  122. Pelosi G, Bresaola E, Bogina G et al (1996) Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variable. Hum Pathol 27:1124–1134

    CAS  PubMed  Google Scholar 

  123. La Rosa S, Sessa F, Capella C et al (1996) Prognostic criteria in nonfunctioning pancreatic endocrine tumours. Virchows Arch 429:323–333

    PubMed  Google Scholar 

  124. von Herbay A, Sieg B, Schürmann G, Hofmann JW, Betzler M, Otto F (1991) Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations. Gut 32:949–953

    Google Scholar 

  125. Chaudry A, Öberg K, Wilander E (1992) A study of biological behavior on the expression of a proliferating antigen in neuroendocrine tumors of the digestive system. Tumor Biol 13:27–35

    Google Scholar 

  126. Canavese G, Azzoni C, Pizzi S et al (2001) p27: a potential main inhibitor of cell proliferation in digestive endocrine tumors but not a marker of benign behavior. Hum Pathol 32:1094–1101

    CAS  PubMed  Google Scholar 

  127. Shimizu T, Tanaka S, Haruma K et al (2000) Growth characteristics of rectal carcinoid tumors. Oncology 59:229–237

    Google Scholar 

  128. Kujari H, Joensuu H, Klemi P, Asola R, Nordman E (1981) A flow cytometric analysis of 23 carcinoid tumors. Cancer 61:2517–2520

    Google Scholar 

  129. Tsushima K, Nagorney DM, Weiland LH, Lieber MM (1989) The relationship of flow cytometric DNA analysis and clinicopathology in small-intestinal carcinoids. Surgery 105:366–373

    CAS  PubMed  Google Scholar 

  130. Tsioulias G, Muto T, Kubota Y et al (1991) DNA ploidy pattern in rectal carcinoid tumors. Dis Colon Rectum 34:31–36

    CAS  PubMed  Google Scholar 

  131. Rindi G, Kloppel G, Alhman H et al (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449:395–401

    CAS  PubMed  Google Scholar 

  132. Rindi G, Kloppel G, Couvelard A et al (2007) TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 451:757–762

    CAS  PubMed  Google Scholar 

  133. Pape UF, Jann H, Muller-Nordhorn J et al (2008) Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 113:256–265

    PubMed  Google Scholar 

  134. Kubo I, Watanabe H (1971) Neoplastic argentaffin cells in gastric and intestinal carcinomas. Cancer 27:447–454

    CAS  PubMed  Google Scholar 

  135. Proks C, Feit V (1982) Gastric carcinomas with argyrophil and argentaffin cells. Virchows Arch 395:201–206

    CAS  Google Scholar 

  136. Smith DM, Haggit RT (1984) The prevalence and prognostic significance of argyrophil cells in carcinomas of the colon and rectum. Am J Surg Pathol 8:123–128

    PubMed  Google Scholar 

  137. Papotti M, Cassoni P, Volante M, Deghenghi R, Muccioli G, Ghigo E (2001) Ghrelin-producing endocrine tumors of the stomach and intestine. J Clin Endocrinol Metab 86:5052–5059

    CAS  PubMed  Google Scholar 

  138. Rindi G, Savio A, Torsello A et al (2002) Ghrelin expression in gut endocrine growths. J Histochem Cell Biol 117(6):521–525

    Google Scholar 

  139. Bordi C, D’Adda T, Azzoni C, Pilato FP, Caruana P (1995) Hypergastrinemia and gastric enterochromaffin-like cells. Am J Surg Pathol 19(suppl 1):S8–S19

    PubMed  Google Scholar 

  140. Rindi G, Bordi C, Rappel S, La Rosa S, Stolte MS, Solcia E (1996) Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology and behavior. World J Surg 20:168–172

    CAS  PubMed  Google Scholar 

  141. Bordi C, Yu JY, Baggi MT, Davoli C, Pilato FP, Baruzzi G, Gardini G, Zamboni G, Franzin G, Papotti M, et al. (1991) Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases. Cancer 67:663–672

    CAS  PubMed  Google Scholar 

  142. Lechago J, Shah IA (1991) The endocrine digestive system. In: Kovacs K, Asa SL (eds) Functional endocrine pathology. Blackwell, Boston, pp 458–477

    Google Scholar 

  143. Ooi A, Ota M, Katsuda S, Nakanishi I, Sugawara H, Takahashi I (1995) An unusual case of multiple gastric carcinoids associated with diffuse endocrine cell hyperplasia and parietal cell hypertrophy. Endocr Pathol 6:229–237

    PubMed  Google Scholar 

  144. Abraham SC, Carney JA, Ooi A, Choti MA, Argani P (2005) Achlorhydria, parietal cell hyperplasia, and multiple gastric carcinoids: a new disorder. Am J Surg Pathol 29:969–975

    PubMed  Google Scholar 

  145. Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G (1995) Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 425:547–560

    CAS  PubMed  Google Scholar 

  146. Pipeleers-Marichal M, Somers G, Willems G et al (1990) Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 322:723–727

    CAS  PubMed  Google Scholar 

  147. Soga J, Yakuwa Y, Osaka M (1999) Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 5:285–292

    CAS  PubMed  Google Scholar 

  148. Lundqvist M, Wilander E (1987) A study of the histopathogenesis of carcinoid tumors of the small intestine and appendix. Cancer 60:201–206

    CAS  PubMed  Google Scholar 

  149. Lester WM, Gotlieb AI (1991) The cardiovascular system. In: Kovacs K, Asa SL (eds) Functional endocrine pathology. Blackwell, Boston, pp 724–747

    Google Scholar 

  150. Fiocca R, G. R, Capella C et al (1987) Glucagon, glicentin, proglucagon, PYY, PP and proPP-icosa-peptide immunoreactivites of rectal carcinoid tumours and related non-tumour cells. Reg Pep 17:9–29

    Google Scholar 

  151. Bordi C, Azzoni C, D’Adda T, Pizzi S (2002) Pancreatic polypeptide-related tumors. Peptides 23:339–348

    CAS  PubMed  Google Scholar 

  152. Rindi G, Capella C, Solcia E (1999) Pathobiology and classification of digestive endocrine tumors. In: Mignon M, Colombel JF (eds) Recent advances in the pathophysiology of inflammatory bowel disease and digestive endocrine tumors. John Libbey Eurotext, Montrouge-London-Rome, pp 177–191

    Google Scholar 

  153. Sobin LH, Wittekind C (eds) (2002) TNM classification of malignant tumours. Wiley-Liss, New York-Toronto

    Google Scholar 

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Ackowledgements

This work was in part supported by grants from the Italian Ministry of the University and Scientific and Technological Research, the Ministry of Health and the University of Parma (to GR and CB).

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  1. Department of Pathology and Laboratory Medicine, Section of Anatomic Pathology, Università di Parma, Parma, Italy

    Guido Rindi

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  1. Guido Rindi
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  2. Silvia Pizzi
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  3. Tiziana D’Adda
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  4. Cesare Bordi
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Correspondence to Guido Rindi .

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  1. Dept. Laboratory Medicine & Pathology, Mayo Clinic, First Street SW 200, Rochester, 55905, U.S.A.

    Ricardo V. Lloyd

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Rindi, G., Pizzi, S., D’Adda, T., Bordi, C. (2010). Endocrine Tumors of the Gastrointestinal System. In: Lloyd, R. (eds) Endocrine Pathology:. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1069-1_16

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