Ghrelin Expression in Neuroendocrine Tumours of the Gastrointestinal Tract with Multiple Endocrine Neoplasia Type 1

Abstract

Ghrelin is a novel gastrointestinal-brain hormone that was first described by Kojima et al. as a growth-hormone-releasing peptide. It can be isolated and purified from different tissues. Evidence of antiproliferative effects in neoplastic cells (binding to normal and neoplastic tissues) supports the hypothesis that ghrelin also plays an important role in endocrine regulation. Whether ghrelin may be involved in formation of neuroendocrine tumours (NET) of the gastrointestinal tract (GIT) in cases of MEN-1 is under discussion. Over the last sixteen years, 227 patients with GIT NET were treated at our institution. Mutations of the menin gene were identified in twelve patients. Eleven of these tumours (islet cell tumours) were localized in the pancreas and one in the stomach. Tissues from these tumours were resected, fixed in formalin and embedded in paraffin. Sections were examined by immunohistochemistry with a primary antibody for ghrelin. Three out of twelve NET in MEN-1 patients (25 %) showed ghrelin expression by immunohistochemistry. Comparison between ghrelin-positive and ghrelin-negative tumours regarding biological activity, morphological aspects and clinicopathological parameters shows no substantial differences. The reported incidence of ghrelin expression in NET of the gastrointestinal tract by MEN-1 was not seen in our patients. Whether or not ghrelin has an influence on neuroendocrine tumour development related to deficient menin-genes is unknown.

Key words

Ghrelin - Neuroendocrine tumours - Multiple endocrine neoplasia type I (MEN I)

References

• 1 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. .  Nature. 1999;  402 656-660
• 2 Date Y, Kojima M, Hosada H, Sawaguchi A, Mondal M S, Suganuma T, Matsukura S, Kangawa K, Nakazato M. .  Endocrinology. 2000;  141 4255-4261
• 3 Dornonville de la Cour C, Bjorkqvist M, Sandvik A K, Bakke I, Zhao C M, Chen D, Hakanson R. .  Regul Pept. 2001;  99 141-150
• 4 Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M. .  J Clin Endocrinol Metab. 2002;  87 1300-1308
• 5 Papotti M, Cassoni P, Volante M, Deghenghi R, Muccioli G, Ghigo E. .  J Clin Endocrinol Metab. 2001;  86 5052-5059
• 6 Iwakura H, Hosoda K, Doi R, Komoto I, Nishimura H. et al . .  J Clin Endocrinol Metab. 2002;  87 4885-4888
• 7 Ukkola O. .  Eur J Clin Invest. 2003;  33 183-185
• 8 Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein H H, Tschöp M, Klein J. .  Horm Metab Res. 2002;  34 640-645
• 9 Seoane L M, Tovar S, Baldelli R, Arvat E, Ghigo E, Casanueva F F, Dieguez C. .  Eur J Endocrinol. 2000;  143 R7-R9
• 10 Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori M, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K. .  J Clin Endocrinol Metab. 2000;  85 4908-4911
• 11 Schmidt A, Maier C, Schaller G, Nowotny P, Bayerle-Eder M, Buranyi B, Luger A, Woltz M. .  Horm Metab Res. 2004;  36 174-177
• 12 Locatelli V, Rossoni G, Schweiger F, Torsello A, De Gennaro-Colonna V, Bernareggi M, Deghenghi R, Muller E E, Berti F. .  Endocrinology. 1999;  140 4024-4031
• 13 Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. .  Am J Physiol Regul Integr Comp Physiol. 2001;  1280 1483-1487
• 14 Broglio F, Benso A, Valetto M R, Gottero C, Quaranta L, Podio V, Arvat E, Bobbio M, Bisi G, Ghigo E. .  Endocrine. 2001;  14 105-108
• 15 Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujima M, Nijima M, Fujina M A, Kasuga M. .  Gastroenterology. 2001;  120 337-345
• 16 Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely A J, Deghenghi R, Ghigo E. .  J Clin Endocrinol Metab. 2001;  81 5083-5086
• 17 van der Lely A J, Tschop M, Heiman M L, Ghigo E. .  Endocr Rev. 2004;  25 426-457