Skip to main content
SpringerLink
Log in

Calcitonin immunoreactivity in neoplastic and hyperplastic parathyroid glands: an immunohistochemical study

  • Clinical Research
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Background

Previous studies have established that calcitonin (CT) and the calcitonin generelated peptide (CGRP) are synthesized and stored in subsets of hyperplastic parathyroid cells that also contain chromogranin B (Schmid, KW, et al. Lab Invest 73:90, 1995). The purpose of the current study was to determine whether other generic but variably expressed neuroendocrine markers, i.e., synaptophysin (SYN) and CD57 (Leu7), are also present in normal, hyperplastic, and neoplastic parathyroid tissue and to assess their relationships to the presence of CT.

Design

Immunoperoxidase stains for chromogranin A (CgA), chromogranin B (CgB), SYN CD57, and CT were performed on 54 hyperplastic, 17 neoplastic (adenoma), and 16 normal parathyroid glands. Sequential sections were stained with antibodies to CgA, CgB, SYN, CD57, and CT using standard avidin-biotin-peroxidase techniques. Results: CgA was diffusely expressed in all normal, hyperplastic, and neoplastic glands. In hyperplasia, CgB was variably expressed in 6 cases (11%), SYN in 6 (11%), CD57 in 15 (28%), and CT in 8 (15%). In adenomas, CgB was variably expressed in 3 (17%), SYN in 3 (17%)., CD57 in 4 (23%), and CT in 4 (23%). All normal glands were negative for CgB, SYN, and CT, while CD57 was variably expressed in 17%. Of the 12 glands that were CT positive, 8 were also positive for CgB, 2 for SYN, and 9 for CD57. Four glands that were strongly and diffusely positive for CT were CgB and SYN negative. Conclusions: CgB, SYN, and CD57 are markers for subsets of hyperplastic and neoplastic parathyroid glands. CT is also expressed in a significant proportion of hyperplastic and neoplastic parathyroid glands, and may be independent of the presence of CgB, SYN, or DD57. The significance of these findings in relationship to the abnormal calcium metabolism in patients with parathyroid hyperplasia remains to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 1.Helle KB. Some chemical and physical properties of the soluble protein fraction of bovine adrenal chromaffin granules. Mol Pharmacol 2:298–310, 1966.

    PubMed  CAS  Google Scholar 

  2. 2.Smith AD, Winkler H. Purification and properties of an acidic protein from chromaffin granules of bovine adrenal medulla. Biochem J 103:483–492, 1967.

    PubMed  CAS  Google Scholar 

  3. 3.Smith WJ, Kirschner N. A specific soluble protein from the catecholamine storage vesicles of bovine adrenal medulla. I. Purification and chemical characterization. Mol Pharmacol 3:52–62, 1967.

    PubMed  CAS  Google Scholar 

  4. 4.Banks, P, Helle KB, Mayor D. Evidence for the presence of chromogranin-like protein in bovine splenic nerve granules. Mol Pharmacol 5:210–212, 1969.

    PubMed  CAS  Google Scholar 

  5. 5.Bartlett SF, Lagercrantz H, Smith AD. Gel electrophoresis of soluble and insoluble proteins of noradrenergic vesicles from ox splenic nerve: a comparison with proteins of adrenal chromaffin granules. Neuroscience 1:339–344, 1976.

    Article  PubMed  CAS  Google Scholar 

  6. 6.Fischer-Colbrie R, Lassmann H, Hagn C, Winkler H. Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissues. Neuroscience 16:547–555, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. 7.O'Connor DT, Burton D, Deftos LJ. Chromogranin A: immunohistology reveals its universal occurrence in normal polypeptide hormone producing endocrine glands. Life Sci 33: 1657–1663, 1983.

    Article  PubMed  Google Scholar 

  8. 8.Cohn DV, Zangerle R, Fischer-Colbrie R, et al. Similarity of secretory protein I from parathyroid gland to chromogranin A from adrenal medulla. Proc Natl Acad Sci USA 79:6045–6059, 1982.

    Article  Google Scholar 

  9. 9.Lloyd RV, Wilson BS. Specific endocrine tissue marker defined by monoclonal antibody. Science 222:628–630, 1983.

    Article  PubMed  CAS  Google Scholar 

  10. 10.O'Connor DT, Burton D, Deftos LJ. Immunoreactive human chromogranin A in diverse polypeptide hormone producing human tumors and normal endocrine tissues. J Clin Endocrinol Metab 57:1084–1086, 1983.

    Article  PubMed  Google Scholar 

  11. 11.Wilson BS, Lloyd RV. Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol 115:458–468, 1984.

    PubMed  CAS  Google Scholar 

  12. 12.Schmid KW, Weiler R, Xu RW, Hogue-Angeletti R, Fischer-Colbrie R, Winkler H. An immunological study on chromogranin A and B in human endocrine and nervous tissues. Histochem J 21:365–373, 1989.

    Article  PubMed  CAS  Google Scholar 

  13. 13.Lloyd RV, Cano M, Rosa P, Hille A, Huttner WB. Distribution of chromogranin, A and secretogranin I (chromogranin B) in neuroendocrine cells and tumors. Am J Pathol 130:296–304, 1988.

    PubMed  CAS  Google Scholar 

  14. 14.Oka T, Yoshioka T, Shrestha GR, et al. Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism. Virchows Arch A Pathol Anat Histopathol 413:53–60, 1988.

    Article  PubMed  CAS  Google Scholar 

  15. 15.Schmid KW, Hittmair A, Ladurner D, Sandbichler P, Gasser R, Totsch M. Chromogranin A and B in parathyroid tissue of cases of primary hyperparathyroidism: an immunohistochemical study. Virchows Arch A Pathol Anat Histopathol 418:295–299, 1991.

    Article  PubMed  CAS  Google Scholar 

  16. 16.Wiedenmann B, Waldherr R, Buhr H, Hille A, Rosa P, Huttner WB. Identification of gastroenteropancreatic neuroendocrine cells in normal and neoplastic human tissue with antibodies against synaptophysin, chromograin A, secretogranin I (chromogranin B), and secretogranin II. Gastroenterology 95:1364–1374, 1988.

    PubMed  CAS  Google Scholar 

  17. 17.Lloyd RV, Jin L, Fields K. Detection of chromogranins A and B in endocrine tissues with radioactive and biotinylated oligonucleotide probes. Am J Surg Pathol 14:35–43, 1990.

    Article  PubMed  CAS  Google Scholar 

  18. 18.Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H. Chromogranin A, B and C in human adrenal medulla and endocrine tissues. Lab Invest 55:405–411, 1986.

    PubMed  CAS  Google Scholar 

  19. 19.Lassmann H, Hagn C, Fischer-Colbrie R, Winkler H. Presence of chromogranin A, B and C in bovine endocrine and nervous tissues: a comparative immunohistochemical study. Histochem J 18:380–386, 1986.

    Article  PubMed  CAS  Google Scholar 

  20. 20.Rindi G, Buffa R, Sessa F, Tortora O, Solcia E. Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules. Histochemistry 85:19–28, 1986.

    Article  PubMed  CAS  Google Scholar 

  21. 21.Wiedenmann B, Huttner WB. Synaptophysin and chromogranins/secretogranins—widespread constitutents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch B Cell Pathol Incl Mol Pathol 58:95–121, 1989.

    PubMed  CAS  Google Scholar 

  22. 22.Schmid KW, Morgan JM, Baumert M, Fischer-Colbrie R, Bocker W, Jasani B. Calcitonin and calcitonin gene related peptide mRNA detection in a population of hyperplastic parathyroid cells also expressing chromogranin B. Lab Invest 73:90–95, 1995.

    PubMed  CAS  Google Scholar 

  23. 23.Friedman PA. Mechanisms of renal calcium transport. Exp Nephrol 8:343–350, 2000.

    Article  PubMed  CAS  Google Scholar 

  24. 24.Solimando DA. Overview of hypercalcemia of malignancy. Am J Health Syst Pharm 58 Suppl 3:S4–7, 2001.

    Google Scholar 

  25. 25.Silver J, Kilav R, Naveh-Many T. Mechanisms of secondary hyperparathyroidism. Am J Physiol Renal Physiol 283:367–376, 2002.

    Google Scholar 

  26. 26.Zaidi M, Inzerillo AM, Moonga BS, Bevis PJR, Huang CL. Forty years of calcitonin—where are we now? A tribute to the work of Iain Macintyre, FRS. Bone 30:655–663, 2002.

    Article  PubMed  CAS  Google Scholar 

  27. 27.O'Rahilly R, Muller F. Human embryology and teratology. 2nd ed. Willey-Liss, New York, 1996, pp. 320–326.

    Google Scholar 

  28. 28.Patey M, Flamen JB, Caron J, Delisle MJ, Delemer B, Pluot M. Bilateral thyroid and ultimobranchial medullary carcinoma. Endocr Pathol 7:349–354, 1996.

    PubMed  Google Scholar 

  29. 29.Lloyd RV, Icangelo A, Eiden LE, Cano M, Jin L, Grimes M. Chromogranin A and B messenger ribonucleic acids in pituitary and other normal and neoplastic human endocrine tissues. Lab Invest 60:548–556, 1989.

    PubMed  CAS  Google Scholar 

  30. Unsicker K. Innervation of endocrine tissues. In: Motta PM ed. Ultrastructure of endocrine cells and tissue. Vol 28 Amsterdam: Martinus Nijhoff Publishers, 1984, pp. 322–330.

    Google Scholar 

  31. Luts L, Bergenfelz A, Alumets J, Sundler F. Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas. Eur J Endocrinol 133:543–551, 1995.

    Article  PubMed  CAS  Google Scholar 

  32. 32.Mortimer ST, Hanley DA, Stell WK. Immunohistochemical identification of calcitonin gene-related peptide and substance P in nerves of the bovine parathyroid gland. Cell Tissue Res 261:339–345, 1990.

    Article  PubMed  CAS  Google Scholar 

  33. 33.Buffa R, Rindi G, Sessa F, et al. Synaptophysin immunoreactivity and small clear vesicles in neuroendocrine cells and related tumors. Mol Cell Probes 1:367–381, 1987.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology & Surgery, University of Massachusetts Medical School, Worcester, MA

    Ashraf Khan MD & Nilima A. Patwardhan MD

  2. Department of Pathology, New England Medical Center, Boston, MA

    Arthur S. Tischler MD

  3. Department of Pathology, Rhode Island Hospital, Providence, RI

    Ronald A. Delellis MD

Authors
  1. Ashraf Khan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arthur S. Tischler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nilima A. Patwardhan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronald A. Delellis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashraf Khan MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, A., Tischler, A.S., Patwardhan, N.A. et al. Calcitonin immunoreactivity in neoplastic and hyperplastic parathyroid glands: an immunohistochemical study. Endocr Pathol 14, 249–255 (2003). https://doi.org/10.1007/s12022-003-0017-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-003-0017-z

Key Words

Search

Navigation