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. 1991 Dec 14;303(6816):1506–1509. doi: 10.1136/bmj.303.6816.1506

Parathyroid hormone related protein and hypercalcaemia in breast cancer.

N J Bundred 1, W A Ratcliffe 1, R A Walker 1, S Coley 1, J M Morrison 1, J G Ratcliffe 1
PMCID: PMC1671803  PMID: 1782489

Abstract

OBJECTIVE--To see whether parathyroid hormone related protein has a humoral role in breast cancer. DESIGN--Plasma concentrations and tumour expression of parathyroid hormone related protein were determined (by two site immunoradiometric assay and immunohistochemistry respectively) in women with breast cancer and related to the presence of bone metastases and serum calcium concentrations. SUBJECTS--Plasma concentrations of parathyroid hormone related protein were measured in 57 women with early breast cancer without apparent bone metastases, 28 women with bone metastases, and 13 women with bone metastases and hypercalcaemia. Tissue positivity for parathyroid hormone related protein was determined retrospectively in 106 primary breast tumours from women without apparent bone metastases and 72 tumours from women with bone metastases, 25 of whom subsequently developed hypercalcaemia. RESULTS--Plasma parathyroid hormone related protein concentrations were detectable (greater than 0.23 pmol/l) in 12 (92%) of the 13 hypercalcaemic patients with bone metastases compared with 10 (36%) of the 28 normocalcaemic patients with bone metastases and five (9%) of the 57 normocalcaemic patients without bone metastases. Parathyroid hormone related protein concentrations were significantly higher in hypercalcaemic than normocalcaemic patients with bone metastases. Tumour staining was positive for parathyroid hormone related protein in 22 (88%) of the 25 primary breast cancers from patients with bone metastases. Tumour staining was positive for parathyroid hormone related protein in 22 (88%) of the 25 primary breast cancers from patients with bone metastases who later developed hypercalcaemia compared with 25 (53%) of the 47 from women in this group who remained normocalcaemic and 55 (52%) of the 106 early breast cancers from women without known metastases. CONCLUSION--Tumour derived parathyroid hormone related protein may have an important humoral role in hypercalcaemia associated with metastatic breast cancer.

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Selected References

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  1. Budayr A. A., Nissenson R. A., Klein R. F., Pun K. K., Clark O. H., Diep D., Arnaud C. D., Strewler G. J. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hypercalcemia. Ann Intern Med. 1989 Nov 15;111(10):807–812. doi: 10.7326/0003-4819-111-10-807. [DOI] [PubMed] [Google Scholar]
  2. Burtis W. J., Brady T. G., Orloff J. J., Ersbak J. B., Warrell R. P., Jr, Olson B. R., Wu T. L., Mitnick M. E., Broadus A. E., Stewart A. F. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med. 1990 Apr 19;322(16):1106–1112. doi: 10.1056/NEJM199004193221603. [DOI] [PubMed] [Google Scholar]
  3. Coleman R. E., Fogelman I., Rubens R. D. Hypercalcaemia and breast cancer--an increased humoral component in patients with liver metastases. Eur J Surg Oncol. 1988 Oct;14(5):423–428. [PubMed] [Google Scholar]
  4. Danks J. A., Ebeling P. R., Hayman J., Chou S. T., Moseley J. M., Dunlop J., Kemp B. E., Martin T. J. Parathyroid hormone-related protein: immunohistochemical localization in cancers and in normal skin. J Bone Miner Res. 1989 Apr;4(2):273–278. doi: 10.1002/jbmr.5650040221. [DOI] [PubMed] [Google Scholar]
  5. Gallacher S. J., Fraser W. D., Patel U., Logue F. C., Soukop M., Boyle I. T., Ralston S. H. Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling. Ann Clin Biochem. 1990 Nov;27(Pt 6):551–556. doi: 10.1177/000456329002700605. [DOI] [PubMed] [Google Scholar]
  6. Henderson J. E., Shustik C., Kremer R., Rabbani S. A., Hendy G. N., Goltzman D. Circulating concentrations of parathyroid hormone-like peptide in malignancy and in hyperparathyroidism. J Bone Miner Res. 1990 Feb;5(2):105–113. doi: 10.1002/jbmr.5650050203. [DOI] [PubMed] [Google Scholar]
  7. Isales C., Carcangiu M. L., Stewart A. F. Hypercalcemia in breast cancer. Reassessment of the mechanism. Am J Med. 1987 Jun;82(6):1143–1147. doi: 10.1016/0002-9343(87)90216-6. [DOI] [PubMed] [Google Scholar]
  8. Kramer S., Reynolds F. H., Jr, Castillo M., Valenzuela D. M., Thorikay M., Sorvillo J. M. Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues. Endocrinology. 1991 Apr;128(4):1927–1937. doi: 10.1210/endo-128-4-1927. [DOI] [PubMed] [Google Scholar]
  9. Legha S. S., Powell K., Buzdar A. U., Blumenschein G. R. Tamoxifen-induced hypercalcemia in breast cancer. Cancer. 1981 Jun 15;47(12):2803–2806. doi: 10.1002/1097-0142(19810615)47:12<2803::aid-cncr2820471208>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  10. Martin T. J. Properties of parathyroid hormone-related protein and its role in malignant hypercalcaemia. Q J Med. 1990 Aug;76(280):771–786. [PubMed] [Google Scholar]
  11. Martin T. J., Suva L. J. Parathyroid hormone-related protein in hypercalcaemia of malignancy. Clin Endocrinol (Oxf) 1989 Nov;31(5):631–647. doi: 10.1111/j.1365-2265.1989.tb01288.x. [DOI] [PubMed] [Google Scholar]
  12. Mundy G. R. Hypercalcemia of malignancy revisited. J Clin Invest. 1988 Jul;82(1):1–6. doi: 10.1172/JCI113555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mundy G. R., Ibbotson K. J., D'Souza S. M., Simpson E. L., Jacobs J. W., Martin T. J. The hypercalcemia of cancer. Clinical implications and pathogenic mechanisms. N Engl J Med. 1984 Jun 28;310(26):1718–1727. doi: 10.1056/NEJM198406283102607. [DOI] [PubMed] [Google Scholar]
  14. Percival R. C., Yates A. J., Gray R. E., Galloway J., Rogers K., Neal F. E., Kanis J. A. Mechanism of malignant hypercalcaemia in carcinoma of the breast. Br Med J (Clin Res Ed) 1985 Sep 21;291(6498):776–779. doi: 10.1136/bmj.291.6498.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Powell G. J., Southby J., Danks J. A., Stillwell R. G., Hayman J. A., Henderson M. A., Bennett R. C., Martin T. J. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res. 1991 Jun 1;51(11):3059–3061. [PubMed] [Google Scholar]
  16. Ralston S. H., Danks J., Hayman J., Fraser W. D., Stewart C. S., Martin T. J. Parathyroid hormone-related protein of malignancy: immunohistochemical and biochemical studies in normocalcaemic and hypercalcaemic patients with cancer. J Clin Pathol. 1991 Jun;44(6):472–476. doi: 10.1136/jcp.44.6.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ratcliffe W. A., Norbury S., Heath D. A., Ratcliffe J. G. Development and validation of an immunoradiometric assay of parathyrin-related protein in unextracted plasma. Clin Chem. 1991 May;37(5):678–685. [PubMed] [Google Scholar]
  18. Sato K., Fujii Y., Kasono K., Tsushima T., Shizume K. Production of interleukin-1 alpha and a parathyroid hormone-like factor by a squamous cell carcinoma of the esophagus (EC-GI) derived from a patient with hypercalcemia. J Clin Endocrinol Metab. 1988 Sep;67(3):592–601. doi: 10.1210/jcem-67-3-592. [DOI] [PubMed] [Google Scholar]
  19. Southby J., Kissin M. W., Danks J. A., Hayman J. A., Moseley J. M., Henderson M. A., Bennett R. C., Martin T. J. Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. Cancer Res. 1990 Dec 1;50(23):7710–7716. [PubMed] [Google Scholar]
  20. Suva L. J., Winslow G. A., Wettenhall R. E., Hammonds R. G., Moseley J. M., Diefenbach-Jagger H., Rodda C. P., Kemp B. E., Rodriguez H., Chen E. Y. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science. 1987 Aug 21;237(4817):893–896. doi: 10.1126/science.3616618. [DOI] [PubMed] [Google Scholar]
  21. van Holten-Verzantvoort A. T., Bijvoet O. L., Cleton F. J., Hermans J., Kroon H. M., Harinck H. I., Vermey P., Elte J. W., Neijt J. P., Beex L. V. Reduced morbidity from skeletal metastases in breast cancer patients during long-term bisphosphonate (APD) treatment. Lancet. 1987 Oct 31;2(8566):983–985. doi: 10.1016/s0140-6736(87)92555-4. [DOI] [PubMed] [Google Scholar]

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