Hereditäre Syndrome neuroendokriner Tumore

D. Kaemmerer; N. Posorski; M. Hommann; R. P. Baum; D. Hörsch

doi:10.1055/s-0033-1350692

Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie, Inhaltsverzeichnis

Zentralbl Chir 2014; 139(4): 415-427
DOI: 10.1055/s-0033-1350692

Übersicht

Georg Thieme Verlag KG Stuttgart · New York

Hereditäre Syndrome neuroendokriner Tumore

Hereditary Syndromes of Neuroendocrine Tumours

D. Kaemmerer

¹Klinik für Allgemeine und Viszeralchirurgie, Zentralklinik Bad Berka GmbH, Bad Berka, Deutschland

,

N. Posorski

²Institut für Humangenetik Core Unit Chip Applikationen, Universitätsklinikum Jena, Jena, Deutschland

,

M. Hommann

¹Klinik für Allgemeine und Viszeralchirurgie, Zentralklinik Bad Berka GmbH, Bad Berka, Deutschland

,

R. P. Baum

³Klinik für Molekulare Radiotherapie/Zentrum für Molekulare Bildgebung (PET/CT), Zentralklinik Bad Berka GmbH, Bad Berka, Deutschland

,

D. Hörsch

⁴Klinik für Innere Medizin/Gastroenterologie und Endokrinologie, Zentralklinik Bad Berka GmbH, Bad Berka, Deutschland

› Institutsangaben

Abstract

Zusammenfassung

Die diffus lokalisierten neuroendokrinen Zellen sind die größte Population an endokrin aktiven Zellen und können als neuroendokrine Tumoren (NET) maligne entarten. In diesem Beitrag werden die wichtigsten hereditären Syndrome, die für endokrine und neuroendokrine Tumoren prädisponieren, dargestellt und diskutiert. Die NET entstehen vorwiegend als sporadische Tumoren. Aktuelle Untersuchungen zur Pathogenese der sporadischen neuroendokrinen Tumoren zeigen einen engen Zusammenhang zwischen hereditären und sporadischen neuroendokrinen Tumoren auf. Im Rahmen von hereditären Syndromen wie den multiplen endokrinen Neoplasien können endokrine und neuroendokrine Tumoren sowie nicht endokrine Neoplasien auftreten. Um diese Syndrome frühzeitig zu erkennen, ist die Kenntnis der prädisponierenden Syndrome und ihrer Leitsymptome wichtig. Damit kann nicht nur die individuelle Diagnose und Therapie geplant werden, sondern auch bei erstgradigen Verwandten eine entsprechende frühzeitige Vorsorge eingeleitet werden.

Abstract

Diffuse localised neuroendocrinal cells represent the largest population of endocrinally active cells and can degenerate to malignant neuroendocrine tumours (NET). In this review the most important hereditary syndromes that predispose for endocrine and neuroendocrine tumours are presented and discussed. NET occur mainly as sporadic tumours. Current investigations on the pathogenesis of sporadic neuroendocrine tumours have revealed a close relationship between hereditary and sporadic neuroendocrine tumours. In the course of hereditary syndromes, such as multiple endocrine neoplasia, endocrine and neuroendocrine tumours as well as non-endocrine neoplasias can occur. In order to recognise these syndromes in good time a knowledge of the predisposing syndromes and their cardinal symptoms is essential. In this way not only individualised diagnosis and therapy can be planned but also an appropriate early management of first degree relatives can be initiated.

Schlüsselwörter

neuroendokrine Tumoren - hereditäre Syndrome - MEN-1 - MEN-2 - VHL - Neurofibromatose

Key words

neuroendocrine tumors - hereditary syndromes - MEN-1 - MEN-2 - VHL - neurofibromatosis

Volltext

Referenzen

Literatur
1 Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003; 97: 934-959
2 Jiao Y, Shi C, Edil BH et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 2011; 331: 1199-1203
3 Speel EJ, Scheidweiler AF, Zhao J et al. Genetic evidence for early divergence of small functioning and nonfunctioning endocrine pancreatic tumors: gain of 9Q34 is an early event in insulinomas. Cancer Research 2001; 61: 5186-5192
4 Zhao J, Moch H, Scheidweiler AF et al. Genomic imbalances in the progression of endocrine pancreatic tumors. Genes Chromosomes Cancer 2001; 32: 364-372
5 Bartsch DK, Kersting M, Wild A et al. Low frequency of p 16(INK4a) alterations in insulinomas. Digestion 2000; 62: 171-177
6 Muscarella P, Melvin WS, Fisher WE et al. Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: an analysis of p 16/MTS1 tumor suppressor gene inactivation. Cancer Res 1998; 58: 237-240
7 Serrano J, Goebel SU, Peghini PL et al. Alterations in the p16INK4a/CDKN2A tumor suppressor gene in gastrinomas. J Clin Endocrinol Metab 2000; 85: 4146-4156
8 Oberg K. Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors). Curr Opin Endocrinol Diabetes Obes 2009; 16: 72-78
9 Dammann R, Schagdarsurengin U, Liu L et al. Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic carcinoma. Oncogene 2003; 22: 3806-3812
10 Dammann R, Schagdarsurengin U, Strunnikova M et al. Epigenetic inactivation of the Ras-association domain family 1 (RASSF1A) gene and its function in human carcinogenesis. Histol Histopathol 2003; 18: 665-677
11 Wang Y, Ozawa A, Zaman S et al. The tumor suppressor protein menin inhibits AKT activation by regulating its cellular localization. Cancer Res 71: 371-382
12 Lollgen RM, Hessman O, Szabo E et al. Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer 2001; 92: 812-815
13 Fujimori M, Ikeda S, Shimizu Y et al. Accumulation of beta-catenin protein and mutations in exon 3 of beta-catenin gene in gastrointestinal carcinoid tumor. Cancer Res 2001; 61: 6656-6659
14 Fujiki K, Duerr EM, Kikuchi H et al. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology 2008; 135: 907-916 916.e901–e902
15 Kidd M, Modlin IM, Mane SM et al. The role of genetic markers–NAP1L1, MAGE-D2, and MTA1–in defining small-intestinal carcinoid neoplasia. Ann Surg Oncol 2006; 13: 253-262
16 Posorski N, Kaemmerer D, Ernst G et al. Localization of sporadic neuroendocrine tumors by gene expression analysis of their metastases. Clin Exp Metastasis 2011; 28: 637-647
17 Begum N, Maasberg S, Plockinger U et al. [Neuroendocrine Tumours of the GI Tract – Data from the German NET Registry.]. Zentralbl Chir 2012; [Epub ahead of print]
18 Anlauf M, Gerlach P, Schott M et al. [Pathology of neuroendocrine neoplasms]. Chirurg 82: 567-573
19 Volante M, Righi L, Berruti A et al. The pathological diagnosis of neuroendocrine tumors: common questions and tentative answers. Virchows Arch 458: 393-402
20 Erlic Z, Neumann HP. Familial pheochromocytoma. Hormones (Athens) 2009; 8: 29-38
21 Moldawer MP, Nardi GL, Raker JW. Concomitance of multiple adenomas of the parathyroids and pancreatic islets with tumor of the pituitary: a syndrome with a familial incidence. Am J Med Sci 1954; 228: 190-206
22 Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med 1954; 16: 363-371
23 Carney JA. Familial multiple endocrine neoplasia: the first 100 years. Am J Surg Pathol 2005; 29: 254-274
24 Lairmore TC, Piersall LD, DeBenedetti MK et al. Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1). Ann Surg 2004; 239: 637-645
25 Larsson C, Skogseid B, Oberg K et al. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 1988; 332: 85-87
26 Underdahl LO, Woolner LB, Black BM. Multiple endocrine adenomas; report of 8 cases in which the parathyroids, pituitary and pancreatic islets were involved. J Clin Endocrinol Metab 1953; 13: 20-47
27 Huang J, Gurung B, Wan B et al. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 2012; 482: 542-546
28 Lemmens I, Van de Ven WJ, Kas K et al. Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Hum Mol Genet 1997; 6: 1177-1183
29 Agarwal SK, Kester MB, Debelenko LV et al. Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 1997; 6: 1169-1175
30 Falchetti A, Morelli A, Amorosi A et al. Allelic loss in parathyroid tumors from individuals homozygous for multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 1997; 82: 2278-2282
31 Giraud S, Zhang CX, Serova-Sinilnikova O et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 1998; 63: 455-467
32 Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 2008; 29: 22-32
33 Trump D, Farren B, Wooding C et al. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 1996; 89: 653-669
34 Agha A, Carpenter R, Bhattacharya S et al. Parathyroid carcinoma in multiple endocrine neoplasia type 1 (MEN1) syndrome: two case reports of an unrecognised entity. J Endocrinol Invest 2007; 30: 145-149
35 Bollerslev J, Marcocci C, Sosa M et al. Current evidence for recommendation of surgery, medical treatment and vitamin D repletion in mild primary hyperparathyroidism. Eur J Endocrinol 2011; 165: 851-864
36 Khan A, Grey A, Shoback D. Medical management of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009; 94: 373-381
37 Waldmann J, Lopez CL, Langer P et al. Surgery for multiple endocrine neoplasia type 1-associated primary hyperparathyroidism. Br J Surg 2010; 97: 1528-1534
38 Pieterman CR, van Hulsteijn LT, den Heijer M et al. Primary hyperparathyroidism in MEN1 patients: a cohort study with longterm follow-up on preferred surgical procedure and the relation with genotype. Ann Surg 255: 1171-1178
39 Benya RV, Metz DC, Venzon DJ et al. Zollinger-Ellison syndrome can be the initial endocrine manifestation in patients with multiple endocrine neoplasia-type I. Am J Med 1994; 97: 436-444
40 Powell AC, Alexander HR, Pingpank JF et al. The utility of routine transcervical thymectomy for multiple endocrine neoplasia 1-related hyperparathyroidism. Surgery 2008; 144: 878-883
41 Edis AJ, Levitt MD. Supernumerary parathyroid glands: implications for the surgical treatment of secondary hyperparathyroidism. World J Surg 1987; 11: 398-401
42 Carty SE, Helm AK, Amico JA et al. The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1. Surgery 1998; 124: 1106-1113
43 Mignon M, Ruszniewski P, Podevin P et al. Current approach to the management of gastrinoma and insulinoma in adults with multiple endocrine neoplasia type I. World J Surg 1993; 17: 489-497
44 Levy-Bohbot N, Merle C, Goudet P et al. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol 2004; 28: 1075-1081
45 Machens A, Schaaf L, Karges W et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol 2007; 67: 613-622
46 Kann PH, Balakina E, Ivan D et al. Natural course of small, asymptomatic neuroendocrine pancreatic tumours in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study. Endocr Relat Cancer 2006; 13: 1195-1202
47 Camera L, Paoletta S, Mollica C et al. Screening of pancreaticoduodenal endocrine tumours in patients with MEN 1: multidetector-row computed tomography vs. endoscopic ultrasound. Radiol Med 116: 595-606
48 Adkisson CD, Stauffer JA, Bowers SP et al. What extent of pancreatic resection do patients with MEN-1 require?. JOP 2012; 13: 402-408
49 Scheithauer BW, Laws jr. ER, Kovacs K et al. Pituitary adenomas of the multiple endocrine neoplasia type I syndrome. Semin Diagn Pathol 1987; 4: 205-211
50 Brauckhoff M, Dralle H. [Recurrent operations on the adrenal glands]. Chirurg 2005; 76: 227-237
51 Brauckhoff M, Nguyen Thanh P, Bar A et al. [Subtotal bilateral adrenalectomy preserving adrenocortical function]. Chirurg; 2003; 74: 646-651
52 Sachithanandan N, Harle RA, Burgess JR. Bronchopulmonary carcinoid in multiple endocrine neoplasia type 1. Cancer 2005; 103: 509-515
53 Manie S, Santoro M, Fusco A et al. The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet 2001; 17: 580-589
54 Santoro M, Melillo RM, Carlomagno F et al. Minireview: RET: normal and abnormal functions. Endocrinology 2004; 145: 5448-5451
55 Takaya K, Yoshimasa T, Arai H et al. Expression of the RET proto-oncogene in normal human tissues, pheochromocytomas, and other tumors of neural crest origin. J Mol Med (Berl ) 1996; 74: 617-621
56 Takahashi M, Asai N, Iwashita T et al. Molecular mechanisms of development of multiple endocrine neoplasia 2 by RET mutations. J Intern Med 1998; 243: 509-513
57 Inabnet WB, Caragliano P, Pertsemlidis D. Pheochromocytoma: inherited associations, bilaterality, and cortex preservation. Surgery 2000; 128: 1007-1011
58 Bergholm U, Adami HO, Bergstrom R et al. Long-term survival in sporadic and familial medullary thyroid carcinoma with special reference to clinical characteristics as prognostic factors. The Swedish MTC Study Group. Acta Chir Scand 1990; 156: 37-46
59 Bergholm U, Adami HO, Telenius-Berg M et al. Incidence of sporadic and familial medullary thyroid carcinoma in Sweden 1959 through 1981. A nationwide study in 126 patients. Swedish MCT Study Group. Acta Oncol 1990; 29: 9-15
60 Eng C, Clayton D, Schuffenecker I et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 1996; 276: 1575-1579
61 Rodriguez JM, Balsalobre M, Ponce JL et al. Pheochromocytoma in MEN 2A syndrome. Study of 54 patients. World JSurg 2008; 32: 2520-2526
62 Modigliani E, Vasen HM, Raue K et al. Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The European Study Group. J Intern Med 1995; 238: 363-367
63 Kloos RT, Eng C, Evans DB et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009; 19: 565-612
64 Seri M, Celli I, Betsos N et al. A Cys634Gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis. Clin Genet 1997; 51: 86-90
65 Wray CJ, Rich TA, Waguespack SG et al. Failure to recognize multiple endocrine neoplasia 2B: more common than we think?. Ann Surg Oncol 2008; 15: 293-301
66 Marinoni I, Pellegata NS. p 27kip1: a new multiple endocrine neoplasia gene?. Neuroendocrinology 2011; 93: 19-28
67 Taguchi R, Yamada M, Horiguchi K et al. Haploinsufficient and predominant expression of multiple endocrine neoplasia type 1 (MEN1)-related genes, MLL, p 27Kip1 and p 18Ink4C in endocrine organs. Biochem Biophys Res Commun 2011; 415: 378-383
68 Alevizaki M, Stratakis CA. Multiple endocrine neoplasias: advances and challenges for the future. J Int Med 2009; 266: 1-4
69 Almeida MQ, Stratakis CA. Solid tumors associated with multiple endocrine neoplasias. Cancer Genet Cytogenet 2010; 203: 30-36
70 Lodish MB, Stratakis CA. Rare and unusual endocrine cancer syndromes with mutated genes. Semin Oncol 2010; 37: 680-690
71 Maher ER, Neumann HP, Richard S. von Hippel-Lindau disease: a clinical and scientific review. Eur J Hum Genet 2011; 19: 617-623
72 Welander J, Soderkvist P, Gimm O. Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer 2011; 18: R253-R276
73 Rasmussen SA, Friedman JM. NF1 gene and neurofibromatosis 1. Am J Epidemiol 2000; 151: 33-40
74 Cawthon RM, Weiss R, Xu GF et al. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 1990; 62: 193-201
75 Garbrecht N, Anlauf M, Schmitt A et al. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer 2008; 15: 229-241
76 Neumann HP, Bausch B, McWhinney SR et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002; 346: 1459-1466