The Histochemical Journal

, Volume 32, Issue 9, pp 551–556 | Cite as

Detection of Chromogranin A in Human Gastric Adenocarcinomas using a Sensitive Immunohistochemical Technique

  • Gunnar Qvigstad
  • Arne K. Sandvik
  • Eiliv Brenna
  • Steinar Aase
  • Helge L. Waldum


Neuroendocrine cells are often disclosed in human gastric adenocarcinomas and may be recognised by their immunoreactivity towards chromogranin A. However, in dedifferentiated neuroendocrine tumour cells, the chromogranin A content may be reduced making it difficult to detect with conventional immunohistochemical methods. We therefore used a sensitive signal amplification technique in order to evaluate chromogranin A immunoreactivity and thus neuroendocrine differentiation in 40 gastric adenocarcinomas.

Neuroendocrine cells were visualised by means of a monoclonal chromogranin A antibody and the avidin–biotin peroxidase complex technique, without and with addition of tyramide signal amplification. Double immunohistochemistry towards chromogranin A and Ki-67 were used to disclose proliferation in the neoplastic cells.

A marked increase in the number of carcinomas containing chromogranin A-immunoreactive neoplastic cells was noted when applying the tyramide signal amplification technique. In addition, the number of immunoreactive cells within each tumour increased, and in some cases almost all the neoplastic cells became immunoreactive. Chromogranin A-immunoreactive tumour cells showing signs of proliferation were found in the majority of these carcinomas.

In conclusion, we have disclosed widespread immunoreactivity towards chromogranin A in a proportion of gastric adenocarcinomas when enhancing the signal with tyramide signal amplification. Neuroendocrine differentiation is thus a common finding in gastric carcinomas when using sensitive methods.


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  1. Adams JC (1992) Biotin amplification of biotin and horseradish peroxidase signals in histochemical stains. J Histochem Cytochem 40: 1457–1463.Google Scholar
  2. Balaton AJ, Galet BA (1998) Detection of chromogranin A mRNA in small cell lung carcinoma using a new, highly sensitive in situ hybridization method with a non-radioisotope oligonucleotide probe. Cancer 83: 1469–1470.Google Scholar
  3. Bensch KG, Corrin B, Pariente R, Spencer H (1968) Oat-cell carcinoma of the lung. Its origin and relationship to bronchial carcinoid. Cancer 22: 1163–1172.Google Scholar
  4. Berner A, Nesland JM (1991) Endocrine profile in gastric carcinomas. An immunohistochemical study. Histol Histopathol 6(3): 317–323.Google Scholar
  5. Burry RW (2000) Specificity controls for immunocytochemical methods. J Histochem Cytochem 48(2): 163–166.Google Scholar
  6. Creutzfeldt W, Arnold R, Creutzfeldt C, Deuticke U, Frerichs H, Track NS (1973) Biochemical and morphological investigations of 30 human insulinomas. Correlation between the tumour content of insulin and proinsulin-like components and the histological and ultrastructural appearance. Diabetologia 9: 217–231.Google Scholar
  7. Deftos LJ, Linnoila RI, Carney DN, Burton DW, Leong SS, O'Connor DT, Murray SS, Gazdar AF (1988) Demonstration of Chromogranin A in human neuroendocrine cell lines by immunohistology and immunoassay. Cancer 62: 92–97.Google Scholar
  8. Gould VE, Linnoila RI, Memoli VA, Warren WH (1983) Neuroendocrine cells and neuroendocrine neoplasms of the lung. Pathol Annu 18: 287–330.Google Scholar
  9. Laurén P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand 64: 31–49.Google Scholar
  10. Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643–649.Google Scholar
  11. Linnoila RI, Mulshine JL, Steinberg SM, Funa K, Matthews MJ, Cotelingam JD, Gazdar AF (1988) Neuroendocrine differentiation in endocrine and nonendocrine lung carcinomas. Am J Clin Pathol 90: 641–652.Google Scholar
  12. Merz H, Malisius R, Mannweiler S, Zhou R, Hartmann W, Orscheschek K, Moubayed P, Feller AC (1995) ImmunoMax. A maximized immunohistochemical method for the retrieval and enhancement of hidden antigens. Lab Invest 73: 149–156.Google Scholar
  13. Nevalainen TJ, Laurén PA (1984) Endocrine cells in gastric carcinoma. Tumor Res 19: 21–24.Google Scholar
  14. Ooi A, Hayashi H, Katsuda S, Nakanishi I (1992) Gastric carcinoma cells with endocrine differentiation show no evidence of proliferation. Hum Pathol 23: 736–741.Google Scholar
  15. Ooi A, Mai M, Ogino T, Ueda H, Kitamura T, Takahashi Y, Kawahara E, Nakanishi I (1988) Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance. Cancer 62: 1096–1104.Google Scholar
  16. Qvigstad G, Falkmer S, Westre B, Waldum HL (1999) Clinical and histopathological tumour progression in ECL cell carcinoids ('ECLomas'). APMIS 107: 1085–1093.Google Scholar
  17. 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. Gastroenterology 104: 994–1006.Google Scholar
  18. Sumiyoshi Y, Shirakusa T, Yamashita Y, Maekawa T, Hideshima T, Sakai T, Kawahara K, Kikuchi M (1998) Detection of chromogranin A mRNAin small cell lung carcinoma using a new, highly sensitive in situ hybridization method with a non-radioisotope oligonucleotide probe. Cancer 82: 468–473.Google Scholar
  19. Waldum HL, Haugen OA, Isaksen C, Mescei R, Sandvik AK (1991) Are diffuse gastric carcinomas neuroendocrine tumours (ECL-omas)? Eur J Gastroenterol Hepatol 3: 245–249.Google Scholar
  20. Waldum HL, Rørvik H, Brenna E (1996) The gastrointestinal tract and the lungs. Similarities with particular emphasis on the neuroendocrine cells. Sarcoidosis Vasc Diffuse Lung Dis 13(1): 63–65.Google Scholar
  21. Waldum HL, Aase S, Kvetnoi I, Brenna E, Sandvik AK, Syversen U, Johnsen G, Vatten L, Polak JM (1998) Neuroendocrine differentiation in human gastric carcinomas. Cancer 83(3): 435–444.Google Scholar
  22. Whitehead R, Cosgrove C (1979) Mucins and carcinoid tumours. Pathology 11: 473–478.Google Scholar
  23. Wiedorn KH, Kühl H, Galle J, Caselitz J, Vollmer E (1999) Comparison of in situ hybridization, direct and indirect in situ PCR as well as tyramide signal amplification for the detection of HPV. Histochem Cell Biol 111(2): 89–95.Google Scholar
  24. Wilson BS, Lloyd RV (1984) Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115: 458–468.Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Gunnar Qvigstad
    • 1
    • 2
  • Arne K. Sandvik
    • 1
  • Eiliv Brenna
    • 2
  • Steinar Aase
    • 3
    • 4
  • Helge L. Waldum
    • 2
  1. 1.Department of Physiology and Biomedical EngineeringNorwegian University of Science and Technology, University HospitalTrondheimNorway
  2. 2.Department of Intra-Abdominal DiseasesNorwegian University of Science and Technology, University HospitalTrondheimNorway
  3. 3.Department of Laboratory MedicineNorwegian University of Science and Technology, University HospitalTrondheimNorway
  4. 4.Department of Pathology, Faculty of DentistryUniversity of OsloNorway

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