Virchows Archiv A

, Volume 411, Issue 3, pp 205–212 | Cite as

Human chorionic gonadotropin in gastric carcinoma

An immunohistochemical study suggesting independent regulation of subunits
  • Masashi Fukayama
  • Yukiko Hayashi
  • Morio Koike


To investigate the production of human chorionic gonadotropin (hCG) in gastric carcinoma, 124 gastric carcinomas and a choriocarcinoma with adenocarcinoma were examined immunohistochemically, using anti-hCGα andβ antibodies. In choriocarcinoma, many trophoblastic cells were synchronously positive for both subunits. In contrast, the distribution of hCG-subunits in gastric carcinoma was unbalanced with hCGα in 39 and hCGβ in 63 cases. 26 cases contained α andβ positive cells, whereas synchronous cells were extremely rare in four cases. Incidences of hCG-subunit-positivities were not different between early and advanced carcinomas. HCGα-positive cells appeared endocrine-like in papillotubular carcinomas and some positive cells were argyrophilic in serial sections in 23 of 39 cases. HCGβ-positive cells were much more frequent in deranged glands, especially of microtubular-mucocellular carcinomas and most were not argyrophilic. In surrounding non-neoplastic mucosa, hCGα-positive cells were more numerous with endocrine-like configurations, but hCGβ-positive cells were rarely present in deranged glands. Although subunit-profile of hCG in gastric carcinomas was different from that of normal, the difference may be quantitative: hCG-subunits may be expressed through an independent mechanism but commonly in gastric mucosa and carcinoma. These results are also discussed in relation to trophoblastic tumours arising in non-trophoblastic tissues.

Key words

Human chorionic gonadotropin Sub-unit Gastric carcinoma Choriocarcinoma Immunohistochemistry 


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  1. Aonuma T, Wakayama H, Takahashi A, Saito K, Miyata M (1986) Choriocarcinoma arising from Barrett's esophagus after esophagocardiectomy for achalasia. Report of an autopsy case. Stomach Intestine 21:83–90Google Scholar
  2. Braunstein GD, Vaitukaitis JL, Carbone PP, Ross GT (1973) Ectopic production of human chorionic gonadotrophin by neoplasms. Ann Intern Med 78:39–45Google Scholar
  3. Braunstein GD, Kamdar V, Rasor J, Swaminathan N, Wade ME (1979) Widespread distribution of a chorionic gonadotropin-like substance in normal human tissues. J Clin Endocrinol Metabol 49:917–925Google Scholar
  4. Braunstein GD, Rasor J, MacCready J, Wade ME (1984) Varying bioactive to immunoactive ratios of the human chorionic gonadotropin-like substance present in normal human tissues. J Clin Endocrinol Metabol 58:170–175Google Scholar
  5. Burnside J, Nagelberg SB, Lippman SS, Weintraub BD (1985) Differential regulation of hCGα andβ subunit mRNAs in JEG-3 choriocarcinoma cells by 8-bromo-cAMP. J Biol Chem 260:12705–12709Google Scholar
  6. Cailani S, Chu M, Nussbaum A, Ostrander M, Christoff N (1976) Human chorionic gonadotrophins (hCG) in non-trophoblastic neoplasms. Assessment of abnormalities of hCG and CEA in bronchogenic and digestive neoplasms. Cancer 38:1684–1686Google Scholar
  7. Fein HG, Rosen SW, Weintraub BD (1980) Increased glycosylation of serum human chorionic gonadotropin and subunits from eutopic and ectopic sources: Comparison with placental and urinary forms. J Clin Endocrinol Metabol 50:1111–1120Google Scholar
  8. Fiddes JC, Talmadge K (1984) Structure, expression, and evolution of the genes for the human glycoprotein hormones. Rec Prog Hormone Res 40:43–78Google Scholar
  9. Fujimoto K, Ogawa M, Saito N, Kosaki G, Minamimura N, Yamamoto T (1980) A novel method of isolation and some characteristic properties of human pancreatic elastases. Biochim Biophys Acta 612:262–267Google Scholar
  10. Fukayama M, Hayashi Y, Takizawa T, Koike M, Endo S, Okumura H (1986a) Glycoprotein hormone alpha-subunit in human stomach. J Histochem Cytochem 34:995–1001Google Scholar
  11. Fukayama M, Hayashi Y, Koike M, Hajikano H, Endo S, Okumura H (1986b) Human chorionic gonadotropin in lung and lung tumors. Immunohistochemical study on unbalanced distribution of subunits. Lab Invest 55:433–443Google Scholar
  12. Fukayama M, Hayashi Y, Koike M (1987) Human chorionic gonadotropin in the rectosigmoid colon. Immunohistochemical study on unbalanced distribution of subunits. Am J Pathol (in press)Google Scholar
  13. Hattori M, Fukase M, Yoshimi H, Matsukura S, Imura H (1978) Ectopic production of human chorionic gonadotropin in malignant tumors. Cancer 42:2328–2333Google Scholar
  14. Hattori M, Yoshimoto Y, Matsukura S, Fujita T (1980) Qualitative and quantitative analyses of human chorionic gonadotropin and its subunits produced by malignant tumors. Cancer 46:355–361Google Scholar
  15. Heitz PU, Kasper M, Klöppel G, Polak JM, Vaitukaitis JL (1983) Glycoprotein-hormone alpha-chain production by pancreatic endocrine tumors: a specific marker for malignancy. Immunocytochemical analysis of tumors of 155 patients. Cancer 51:277–282Google Scholar
  16. Hoshina M, Boothby M, Hussa R, Pattillo R, Camel HM, Boime I (1985) Linkage of human chorionic gonadotrophin and placental lactogen biosynthesis to trophoblast differentiation and tumorigenesis. Placenta 6:163–172Google Scholar
  17. Hussa RO, Fein HG, Pattillo RA, Nagelberg SB, Rosen SW, Weintraub BD, Perini F, Ruddon RW, Cole LA (1986) A distinctive form of human chorionic gonadotropinβ-sub-unit-like material produced by cervical carcinoma cells. Cancer Res 46:1948–1954Google Scholar
  18. Hustin J, Reuter AM, Franchimont P (1985) Immunohistochemical localization of HCG and its subunits in testicular germ cell tumours. Virchows Arch A (Pathol Anat) 406:333–338Google Scholar
  19. Ito H, Tahara E (1983) Human chorionic gonadotropin in human gastric carcinoma. A retrospective immunohistochemical study. Acta Pathol Jpn 33:287–296Google Scholar
  20. Iwaki K, Ogawa M, Tanaka S, Kosaki G (1983a) Radioimmunoassay for human pancreatic chymotrypsin and measurement of serum immunoreactive chymotrypsin contents in various diseases. Res Commun Chem Pathol Pharmacol 40:489–496Google Scholar
  21. Iwaki K, Ogawa M, Kitahara T, Tanaka S, Kosaki G (1983b) Influences of inactivation of trypsin on immunoreactivity and serum immunoreactive trypsin concentration measured by radioimmunoassay. Enzyme 29:153–159Google Scholar
  22. Jagiello G, Mesa-Tejada R (1979) Cross-reactivity of human luteinizing hormone (β-subunit) and a serine protease demonstrated by immunoperoxidase staining in human oocytes. Endocrinology 104:302–306Google Scholar
  23. Japanese Research Society for Gastric Cancer (1979) The general rules for the gastric cancer study in surgery and pathology. 10th ed. Tokyo, Kanehara ShuppanGoogle Scholar
  24. Lauren P (1965) The two histological main types of gastric carcinoma, diffuse and so-called intestinal type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scandinav 64:31–49Google Scholar
  25. Manabe T, Adachi M, Hirao K (1985) Human chorionic gonadotropin in normal, inflammatory, and carcinomatous gastric tissue. Gastroenterology 89:1319–1325Google Scholar
  26. Metz KA, Richter HJ, Leder L-D (1985) Adenocarcinoma of the colon with syncytiotrophoblastic differentiation: differential diagnosis and implication. Path Res Pract 179:419–424Google Scholar
  27. Mori H, Soeda O, Kamano T, Tsunekawa K, Ueda N, Yoshida A, Fukunishi R (1982) Choriocarcinomatous change with immunocytochemically HCG-positive cells in gastric carcinoma of the males. Virchows Arch A (Pathol Anat) 396:141–153Google Scholar
  28. Murata A, Ogawa M, Fujimoto K, Kitahara T, Matsuda Y, Kosaki G (1983) Radioimmunoassay of human pancreatic elastase 1: In vitro interaction of human pancreatic elastase 1 with serum protease inhibitors. Enzyme 30:29–37Google Scholar
  29. Okumura H, Sudo T, Fujisawa M, Namba S, Matsushima S (1976) Purification of subunits from human chorionic gonadotropin and radioimmunoassay. Folia Endocrinol Jpn 52:105–113Google Scholar
  30. Okumura H, Sudo T, Sawai M, Fujisawa M, Hyakawa H (1978) Purification of hCG subunits. Their biological and immunological characterization. Clin Endocrinol 26:509–518Google Scholar
  31. Papapetrou PD, Sakarelou NP, Braouzi H, Fessa P (1980) Ectopic production of human chorionic gonadotropin (hCG) by neoplasms: the value of measurements of immunoreactive hCG in the urine as a screening procedure. Cancer 45:2583–2592Google Scholar
  32. Parsons TF, Bloomfield GA, Pierce JG (1983) Purification of an alternate form of the α subunit of the glycoprotein hormones from bovine pituitaries and identification of its O-linked oligosaccharide. J Biol Chem 258:240–244Google Scholar
  33. Pierce JG, Parsons TF (1981) Glycoprotein hormones: Structure and function. Ann Rev Biochem 50:465–495Google Scholar
  34. Rosen SW, Weintraub BD, Arronson SA (1980) Nonrandom ectopic protein production by malignant cells: direct evidence in vitro. J Clin Endocrinol Metabol 50:834–841Google Scholar
  35. Stanbridge EJ, Rosen SW, Sussman HH (1982) Expression of the α subunit of human chorionic gonadotropin is specifically correlated with tumorigenic expression in human cell hybrids. Proc Natl Acad Sci USA 79:6242–6245Google Scholar
  36. Sternberger LA (1979) Immunocytochemistry. New York, John WileyGoogle Scholar
  37. Tashjian AH Jr, Weintraub BD, Barowsky NJ, Rabson AS, Rosen SW (1973) Subunits of human chorionic gonadotropin: unbalanced synthesis and secretion by clonal cell strains derived from a bronchogenic carcinoma. Proc Natl Acad Sci USA 70:1419–1422Google Scholar
  38. Warner TFCS (1974) Cell hybridization in the genesis of ectopic hormone-secreting tumours. Lancet i:1259–1260Google Scholar
  39. Wasada T, Kato K, Ibayashi H (1979) Ectopic production of human chorionic gonadotropin by malignant neoplasms. Jap J Cancer Clin 25:561–566Google Scholar
  40. Weintraub BD, Rosen SW (1973) Ectopic production of the isolated beta subunit of human chorionic gonadotropin. J Clin Invest 52:3135–3142Google Scholar
  41. Wittekind C, Wachner R, Henke W, von Kleist S (1986) Localization of CEA, HCG, Lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin in gastric cancer and prognosis. Virchows Arch A (Pathol Anat) 409:715–724Google Scholar
  42. Yoshimoto Y, Wolfsen AR, Odell WD (1977) Human chorionic gonadotropin-like substance in non-endocrine tissues of normal subjects. Science 197:575–577Google Scholar
  43. Yoshimoto Y, Wolfsen AR, Hirose F, Odell WD (1979) Human chorionic gonadotropin-like material: Presence in normal human tissues. Am J Obstet Gynecol 134:729–733Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • Masashi Fukayama
    • 1
  • Yukiko Hayashi
    • 1
  • Morio Koike
    • 1
  1. 1.Department of PathologyTokyo Metropolitan Komagome HospitalTokyoJapan

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