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Pancreatic endocrine tumours associated with WDHA syndrome

An Immunohistochemical and electron microscopic study

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Summary

Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed.

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References

  • Abe K, Adachi I, Miyakawa S, Tanaka M, Yamaguchi K, Tanaka N, Kameya T, Shimosato Y (1977) Production of calcionin, adrenocorticotropic hormone, andβ-melanocyte-stimulating hormone in tumors derived from amine precursor uptake and decarboxylation cells. Cancer Res 37:4190–4194

    Google Scholar 

  • Amara SG, Jonas V, Rosenfeld MG (1982) Alternative RNA processing in calcitionin gene expression generates mRNAs encoding different polypeptide products. Nature 298:240–244

    Google Scholar 

  • Bloodworth JMBJ, Greider M (1982) Endocrine pancreas and diabetes mellitus. In: Bloodworth JMBJ (ed). Endocrine pathology. Williams and Wilkins, Baltimore, London, pp 556–631

    Google Scholar 

  • Bloom SR, Christofides ND, Delamaster J, Buell G, Kawashima E (1983) Diarrhoea in vipoma patients associated with cosecretion of a second active peptide (peptide histidine isoleucine) explained by single coding gene. Lancet ii:1163–1165

    Google Scholar 

  • Blundell TL, Humbell RE (1980) Hormone families: pancreatic hormones and homologous growth factor. Nature 287:781–787

    Google Scholar 

  • Capella C, Polak JM, Buffa R, Tapia FJ, Usellini L, Bloom SR, Solcia E (1983) Morphologic patterns and diagnostic criteria of VIP-producing endocrie tumours. Cancer 52:1860–1874

    Google Scholar 

  • Chance RE, Moon NE, Johnson MG (1979) Human pancreatic polypeptide (HPP) and bovine pancreatic polypeptide (BPP). In: Jaffe BM, Behman HR (eds). Methods of Hormone Radioimmunoassay. Academic Press, London, pp 657–672

    Google Scholar 

  • Christofides ND, Yiangou Y, Blank MA, Tatemoto K, Polak JM, Bloom SR (1982) Are peptide histidine isoleucine and vasoactive intestinal peptide co-synthesized in the same pro-hormone? Lancet ii:1398

    Google Scholar 

  • Cox TM, Fagen EA, Hillyard CJ, Allison DJ, Chadwick VS (1979) Role of calcitonin in diarrhoea associated with medullary carcinoma of the thyroid. Gut 20:629–633

    Google Scholar 

  • Galmiche JP, Chayvialle JA, Dubois PM, David L, Descos F, Paulin C, Ducastelle T, Colin R (1980) Carcitonin-producing pancreatic somatostatinoma. Gastroenterology 78:1577–1583

    Google Scholar 

  • Gutniak M, Rosenqvist U, Grimelius L, Lundberg JM, Hökfelt T, Rökaeus A, Rosell S, Lundqvist G, Fahrenkrug J, Sundblad R, Gutniak E (1980) Report on a patient with watery diarrhoea syndrome caused by a pancreatic tumour containing neurotensin, enkephalin and calcitonin. Acta Med Scand 208:95–100

    Google Scholar 

  • Heitz P, Polak JM, Bloom SR, Adrian TE, Pearse AGE (1976) Cellular origin of human pancreatic polypeptide (HPP) in endocrine tumours of the pancreas. Virchows Arch [Cell Pathol] 21:259–265

    Google Scholar 

  • Heitz PU, Kaspar M, Polak JM, Klöppel G (1982) Pancreatic endocrine tumours. Immunohistochemical analysis of 125 tumours. Hum Pathol 13:263–271

    Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) A comparative study of the PAP method and avidin-biotin-complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 75:734–738

    Google Scholar 

  • Itoh N, Obata K, Yanaihara N, Okamoto H (1983) Human preprovasoactive intestinal polypeptide, PHM-27. Nature 304:547–549

    Google Scholar 

  • Jaffe BM, Kopen DF, DeSchryver-Kecskemeti K, Gingerich RL, Greider M (1977) Indomethacin-responsive pancreatic cholera. New Engl J Med 297:817–821

    Google Scholar 

  • Kameya T, Yamaguchi K, Tsumuraya M, Abe K (1982) Morphological features in multiple hormone production by pancreatic endocrine tumours. In: Miyoshi A (ed). Gut peptide and ulcer. Proceedings of Hiroshima Symposium on Gut Peptide and Ulcer. Biomedical Research Foundation, Tokyo, pp 207–214

    Google Scholar 

  • Kameya T, Shimosato Y, Kodama T, Tsumuraya M, Koide T, Yamaguchi K, Abe K (1983a)Peptide hormone production by adenocarcinomas of the lungs; Its morphologic basis and histogenetic consideration. Virchows Arch [Pathol Anat] 400:245–257

    Google Scholar 

  • Kameya T, Bessho T, Tsumuraya M, Yamaguchi K, Abe K, Shimosato Y, Yanaihara N (1983b) Production of gastrin releasing peptide by medullary carcinoma of the thyroid. Virchows Arch [Pathol Anat] 401:99–108

    Google Scholar 

  • Kane MG, O'Dorisio TM, Krejs GJ (1983) Production of secretory diarrhea by intravenous infusions of vasoactive intestinal polypeptide. New Engl J Med 309:1482–1485

    Google Scholar 

  • Larsson LI (1980) On the possible existence of multiple endocrine, paracrine and neurocrine messengers in secretory cell system. Invest Cell Pathol 3:73–85

    Google Scholar 

  • Larsson LI, Schwartz T, Lundqvist G, Chance RE, Sundler F, Rehfeld JF, Grimelius L, Fahrenkrug J, Schaffalitzky de Muckadell O, Moon N (1976) Occurrence of human pancreatic polypeptide in pancreatic endocrine tumours. Am J Pathol 85:675–684

    Google Scholar 

  • Long RG, Bryant MG, Mitchell SJ, Adrian TE, Polak JM, Bloom SR (1981) Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas). Br Med J 282:1767–1770

    Google Scholar 

  • Lundqvist G, Krause U, Larsson LI, Grimelius L, Schaffalitzky de Muckadell O, Fahrenkrug J, Johnson M, Chance RE (1978) A pancreatic-polypeptide-producing tumour associated with the WDHA syndrome. Scand J Gastroenterology 13:715–718

    Google Scholar 

  • Mukai K, Greider MH, Grotting JC, Rosai J (1982) Retrospective study of 77 pancreatic endocrine tumours using immunoperoxidase method. Am J Surg Pathol 6:387–399

    Google Scholar 

  • Nakanishi S, Inoue A, Kita T, Nakamura M, Chang ACY, Cohen SN, Numa S (1979) Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor. Nature 278:423–427

    Google Scholar 

  • Öberg K, Lööf L, Boström H, Grimelius L, Fahrenkrug J, Lundqvist G (1981) Hypersecretion of calcitonin in patients with the Verner-Morrison syndrome. Scand J Gastroent 16:135–144

    Google Scholar 

  • Orci L, Malaisse-Lagae F, Baetens D, Perrelet A (1978) Pancreatic-polypeptide-rich regions in human pancreas. Lancet ii:1200–1201

    Google Scholar 

  • Polak JM, Bloom SR, Adrian TE, Heitz PH, Bryant MG, Pearse AGE (1976) Pancreatic polypeptide in insulinomas, gastrinomas, vipomas and glucagonomas. Lancet i:328–330

    Google Scholar 

  • Rambaud JC, Galian A, Scotto J (1975) Pancreatic cholera (WDHA syndrome): Histochemical and ultrastructural studies. Virchows Arch [Pathol Anat] 367:35–45

    Google Scholar 

  • Roth J, Bendayan M, Orci L (1978) Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. J Histochem Cytochem 26:1074–1081

    Google Scholar 

  • Tatemoto K, Mutt V (1981) Isolation and characterization of the intestinal peptide porcine PHI (PHI-27), a new member of the glucagon-secretion family. Proc Natl Acad Sci USA 78:6603–6607

    Google Scholar 

  • Tsutsumi Y, Osamura Y, Watanabe K, Yanaihara N (1983) Simultaneous immunohistochemical localization of gastrin releasing peptide (GRP) and calcitonin (CT) in human bronchial endocrine type cells. Virchows Arch [Pathol Anat] 400:163–171

    Google Scholar 

  • Yamaguchi K, Abe K, Miyakawa S, Ohnami S, Sakagami M, Yanaihara N (1980a) The presence of macromolecular vasoactive intestinal polypeptide (VIP) in VIP-producing tumours. Gastroenterology 79:687–694

    Google Scholar 

  • Yamaguchi K, Kameya T, Abe K (1980b) Multiple endocrine neoplasia type 1. Clin Endocrinol Metabol 9:261–284

    Google Scholar 

  • Yamaguchi K, Adachi I, Miyakawa S, Abe K, Yanaihara N (1981) Macromolecular forms of somatostatin-producing tumours. In: Japanese Society of Gut hormone (ed), Igakutoshoshuppan Tokyo, pp 228–235

    Google Scholar 

  • Yamaguchi K, Abe K, Kameya T, Adachi I, Taguchi S, Otsubo K, Yanihara N (1983) Production and molecular size heterogeneity of immunoreactive gastrin-releasing peptide in fetal and adult lungs and primary lung tumours. Cancer Res 43:3932–3939

    Google Scholar 

  • Yamaguchi K, Abe K, Otsubo K, Hanieuda C, Suzuki M, Shimada A, Kimura S, Adachi I, Kameya T, Yanaihara N (1984) The WDHA syndrome: clinical and laboratory data on 28 Japanese cases. Peptides 5:415–421

    Google Scholar 

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Authors and Affiliations

  1. Pathology Division, National Cancer Center Research Institute, Tokyo

    Akishi Ooi, Masaru Tsumuraya & Yukio Shimosato

  2. Department of Pathology, Kitasato University, School of Medicine, Kanagawa

    Toru Kameya

  3. Endocrinology Division, National Cancer Center Research Institute, Tokyo

    Ken Yamaguchi & Kaoru Abe

  4. Laboratory of Bioorganic Chemistry, Shizuoka College of Pharmacy, Shizuoka

    Noboru Yanaihara

  5. Department of Pathology, School of Medicine, Kanazawa University, Kanazawa

    Akishi Ooi

Authors
  1. Akishi Ooi
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  2. Toru Kameya
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  3. Masaru Tsumuraya
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  4. Ken Yamaguchi
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  5. Kaoru Abe
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  6. Yukio Shimosato
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  7. Noboru Yanaihara
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Additional information

This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science and Culture, Japan

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Ooi, A., Kameya, T., Tsumuraya, M. et al. Pancreatic endocrine tumours associated with WDHA syndrome. Vichows Archiv A Pathol Anat 405, 311–323 (1985). https://doi.org/10.1007/BF00710067

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  • DOI: https://doi.org/10.1007/BF00710067

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