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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1978 Aug;31(8):784–790. doi: 10.1136/jcp.31.8.784

Histological demonstration of copper and copper-associated protein in chronic liver diseases.

S Jain, P J Scheuer, B Archer, S P Newman, S Sherlock
PMCID: PMC1145407  PMID: 80410

Abstract

Liver copper concentrations in percutaneous biopsy specimens were measured by neutron activation analysis and compared with histological staining for copper by rubeanic acid and rhodanine, and with copper-associated protein stained by orcein. Liver copper concentrations were elevated in 31 of 35 biopsies from patients with primary biliary cirrhosis (PBC), and discrimination between normal and elevated liver copper was correct in 32 of the 35 biopsies by staining with rubeanic acid, and 31 of the 35 by staining with rhodanine. Orcein staining of copper-associated protein was positive in 33 of the 35 biopsies. All 17 biopsy specimens from patients with Wilson's disease had high liver copper concentrations, but only nine had positive staining for copper, and six were orcein positive. Similarly, histological stains gave little indication of the liver copper concentrations in tissue from 16 patients with chronic active hepatitis. Staining of liver sections can be useful in detecting elevation of liver copper in PBC, but not in Wilson's disease, where the absolute concentration must be measured. Excess copper appears to accumulate in the liver in different chemical forms in PBC and Wilson's disease.

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Selected References

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  1. CARTWRIGHT G. E., WINTROBE M. M. COPPER METABOLISM IN NORMAL SUBJECTS. Am J Clin Nutr. 1964 Apr;14:224–232. doi: 10.1093/ajcn/14.4.224. [DOI] [PubMed] [Google Scholar]
  2. Dastur D. K., Manghani D. K. The liver in Wilson's disease. Some histochemical and histological aspects. Indian J Pathol Bacteriol. 1967 Apr;10(2):177–183. [PubMed] [Google Scholar]
  3. Deodhar K. P., Tapp E., Scheuer P. J. Orcein staining of hepatitis B antigen in paraffin sections of liver biopsies. J Clin Pathol. 1975 Jan;28(1):66–70. doi: 10.1136/jcp.28.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Evans G. W., Bubois R. S., Hambidge K. M. Wilson's disease: identification of an abnormal copper-binding protein. Science. 1973 Sep 21;181(4105):1175–1176. doi: 10.1126/science.181.4105.1175. [DOI] [PubMed] [Google Scholar]
  5. Evans G. W. Function and nomenclature for two mammalian copper proteins. Nutr Rev. 1971 Sep;29(9):195–197. doi: 10.1111/j.1753-4887.1971.tb07299.x. [DOI] [PubMed] [Google Scholar]
  6. Fleming C. R., Dickson E. R., Baggenstoss A. H., McCall J. T. Copper and primary biliary cirrhosis. Gastroenterology. 1974 Dec;67(6):1182–1187. [PubMed] [Google Scholar]
  7. Goldfischer S., Sternlieb I. Changes in the distribution of hepatic copper in relation to the progression of Wilson's disease (hepatolenticular degeneration). Am J Pathol. 1968 Dec;53(6):883–901. [PMC free article] [PubMed] [Google Scholar]
  8. HOWELL J. S. Histochemical demonstration of copper in copper-fed rats and in hepatolenticular degeneration. J Pathol Bacteriol. 1959 Apr;77(2):473–484. doi: 10.1002/path.1700770218. [DOI] [PubMed] [Google Scholar]
  9. HUNT A. H., PARR R. M., TAYLOR D. M., TROTT N. G. RELATION BETWEEN CIRRHOSIS AND TRACE METAL CONTENT OF LIVER WITH SPECIAL REFERENCE TO PRIMARY BILIARY CIRRHOSIS AND COPPER. Br Med J. 1963 Dec 14;2(5371):1498–1501. doi: 10.1136/bmj.2.5371.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Irons R. D., Schenk E. A., Lee J. C. Cytochemical methods for copper. Semiquantitative screening procedure for identification of abnormal copper levels in liver. Arch Pathol Lab Med. 1977 Jun;101(6):298–301. [PubMed] [Google Scholar]
  11. Jain S., Scheuer P. J., Samourian S., McGee J. O. A controlled trial of D-penicillamine therapy in primary biliary cirrhosis. Lancet. 1977 Apr 16;1(8016):831–834. doi: 10.1016/s0140-6736(77)92778-7. [DOI] [PubMed] [Google Scholar]
  12. Lindquist R. R. Studies on the pathogenesis of hepatolenticular degeneration. II. Cytochemical methods for the localization of copper. Arch Pathol. 1969 Apr;87(4):370–379. [PubMed] [Google Scholar]
  13. Mallory F. B., Parker F. Fixing and staining methods for lead and copper in tissues. Am J Pathol. 1939 Sep;15(5):517–522.5. [PMC free article] [PubMed] [Google Scholar]
  14. Salaspuro M., Sipponen P. Demonstration of an intracellular copper-binding protein by orcein staining in long-standing cholestatic liver diseases. Gut. 1976 Oct;17(10):787–790. doi: 10.1136/gut.17.10.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shikata T., Uzawa T., Yoshiwara N., Akatsuka T., Yamazaki S. Staining methods of Australia antigen in paraffin section--detection of cytoplasmic inclusion bodies. Jpn J Exp Med. 1974 Feb;44(1):25–36. [PubMed] [Google Scholar]
  16. Sipponen P. Orcein positive hepatocellular material in long-standing biliary diseases. I. Histochemical characteristics. Scand J Gastroenterol. 1976;11(6):545–552. [PubMed] [Google Scholar]
  17. Sipponen P., Salaspuro M. P., Makkonen H. M. Orcein positive hepatocellular material in histological diagnosis of primary biliary cirrhosis. Ann Clin Res. 1975 Aug;7(4):273–277. [PubMed] [Google Scholar]
  18. Smallwood R. A., Williams H. A., Rosenoer V. M., Sherlock S. Liver-copper levels in liver disease: studies using neutron activation analysis. Lancet. 1968 Dec 21;2(7582):1310–1313. doi: 10.1016/s0140-6736(68)91814-x. [DOI] [PubMed] [Google Scholar]
  19. Sternlieb I. Evolution of the hepatic lesion in Wilson's disease (hepatolenticular degeneration). Prog Liver Dis. 1972;4:511–525. [PubMed] [Google Scholar]
  20. Sternlieb I., Scheinberg I. H. Prevention of Wilson's disease in asymptomatic patients. N Engl J Med. 1968 Feb 15;278(7):352–359. doi: 10.1056/NEJM196802152780702. [DOI] [PubMed] [Google Scholar]
  21. Todd A. P., Thorpe M. E., Rosenoer V. M. Tissue copper determinations by neutron activation analysis. J Clin Pathol. 1967 May;20(3):276–279. doi: 10.1136/jcp.20.3.276. [DOI] [PMC free article] [PubMed] [Google Scholar]

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