Surgery Today

, Volume 24, Issue 3, pp 215–220 | Cite as

The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases

  • Norio Kohno
  • Sohei Kitazawa
  • Masaaki Fukase
  • Yoko Sakoda
  • Yoshihiro Kanbara
  • Yoshihiko Furuya
  • Osamu Ohashi
  • Yoshio Ishikawa
  • Yoichi Saitoh
Original Articles

Abstract

The relationship between the expression of parathyroid hormone-related protein (PTHrP) by breast cancer and skeletal metastases, was investigated using a monoclonal antibody against human PTHrP (4133). The immunohistochemical localization of PTHrP was studied in sections of formalin-fixed, paraffin-embeded tissues from 28 breast cancers obtained surgically between 1980 and 1985. Of the 28 patients, 12 developed skeletal metastases, 8 developed lung metastases, and the other 8 were alive and disease-free at the time of this study. Sixteen of the 28 (57%) tumors showed positive immunoreactivity to 4133, the PTHrP positive ratio being 83% in the patients who developed skeletal metastases, 38% in those who developed lung metastases, and 38% in those without recurrence, respectively. Thus, a significantly higher proportion of the patients who developed skeletal metastases were positive for PTHrP than the other two groups (P < 0.05). Furthermore, the level of positive staining was strongly related to positivity for estrogen and progesterone receptors (P < 0.01). These results are consistent with the hypothesis that PTHrP might be necessary for metastases to erode bone and grow in skeletal sites, and its expression could be related to certain hormones.

Key Words

parathyroid hormone-related protein breast cancer skeletal metastases 

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References

  1. 1.
    Galasko CSB (1976) Mechanism of bone destruction in the development of skeletal metastases. Nature 263:507–508PubMedGoogle Scholar
  2. 2.
    Mundy GR, Martin TJ (1983) The hypercalcemia of malignancy: Pathogenesis and management. Metabolism 31:1247–1227Google Scholar
  3. 3.
    Suva LJ, Winslow GA, Wettenhall REH, Hammonds RG, Mosley JM, Jagger HD, Rodda CP, Kemp BE, Rodriguez H, Chen EY, Hudson PJ, Martin TJ, Wood WI (1987) A parathyroid hormonerelated protein implicated in malignant hypercalcemia: Cloning and expression. Science 237:893–896PubMedGoogle Scholar
  4. 4.
    Manngin M, Webb AC, Dreyer BE, Posillico JT, Ikeda K, Weir EC, Stewart AF, Bander NH, Milstone L, Barton DE, Francke U, Broadus AE (1988) Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy Proc Natl Acad Sci USA 85:597–601PubMedGoogle Scholar
  5. 5.
    Stewert AF, Wu T, Goumas D, Burtis WJ, Broadus AE (1987) N-adenylcyclase-stimum terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: Identification of parathyroid hormone-like and parathyroid hormone unlike domains. Biochem Biophys Res Commun 146:672–678PubMedGoogle Scholar
  6. 6.
    Strewler GJ, Stem PH, Jacobs JW, Eveloff J, Klein RF, Leung SC, Roenblatt M, Nissenson RA (1987) Parathyroid hormonelike protein from human renal carcinoma cells structural and functional homology with parathyroid hormone. J Clin Invest 80:1803–1807PubMedGoogle Scholar
  7. 7.
    Southby J, Kissin MW, Danks JA, Hayman JA, Moseley JM, Henderson MA, Bennett RC, Martin TJ (1990) Immunohistochemicallocalization of parathyroid hormone-related protein in human breast cancer. Cancer Res 50:7710–7716PubMedGoogle Scholar
  8. 8.
    Kitazawa S, Fukase M, Kitazawa R, Takenaka A, Gotoh A, Fujita T, Maeda S (1991) Immunohistological evaluation of parathyroid hormone-related protein (PTHrP) in human lung cancer and normal tissue with newly developed monoclonal antibody. Cancer 67:984–989PubMedGoogle Scholar
  9. 9.
    Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting of predefined specificity. Nature 256:495–497PubMedGoogle Scholar
  10. 10.
    Thomus AN, Loken HF, Goldman L (1960) Hypercalcemia of metastatic breast cancer. Surg Forum 16:70–71.Google Scholar
  11. 11.
    Mundy GR, Ibbotson KJ, D'Souza SM (1985) Tumor products and the hypercalcemia of malignancy. J Clin Invest 76:391–394PubMedGoogle Scholar
  12. 12.
    Mansi JL, Brger U, Easton D, McDonnell T, Redding W, Gazet J, McKinna A, Powles TJ, Coombes R (1985) Micrometastasis in bone marrow in patients with primary breast cancer: Evaluation as an early predictor of bone metastasis. J Clin Invest 76:391–394PubMedGoogle Scholar
  13. 13.
    Redding WH, Coombes RC, Monaghan P, Clink HM, Imrie SF, Dearnaley DP, Ormerod MG, Sloane JP, Gazet J, Powles JJ (1983) Detection of micrometastases in patients with primary breast cancer. Lancet 2:1271–1274PubMedGoogle Scholar
  14. 14.
    Untch M, Harback N, Eiermann W (1988) Micrometastasis in bone marrow in patients with breast cancer. Br Med J 296:290Google Scholar
  15. 15.
    Elston CW, Blarney RW, Johnson J (1980) The relationship of estradiol receptor (ER) and histological tumor differentiation with prognosis in human primary breast carcinoma. In: Mouridsen HT, Palshof T (eds) Breast cancer; experimental and clinical aspects. Pergamon, Oxford, p 59Google Scholar
  16. 16.
    Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66PubMedGoogle Scholar
  17. 17.
    Sherry MM, Greco FA, Johnson DH, Hainsworth JD (1986) Metastatic breast cancer confined to the skeletal system: An indolent disease. Am J Med 81:381–386PubMedGoogle Scholar
  18. 18.
    Sherry MM, Greco FA, Johnson DH, Hainsworth JD (1986) Breast cancer with skeletal metastases at initial diagnosis. Cancer 58:178–182PubMedGoogle Scholar
  19. 19.
    Thiede MA, Roden GA (1988) Expression of a calciummobilizing parathyroid hormone-like peptide in lactating mammary tissue. Science 242:278–280PubMedGoogle Scholar
  20. 20.
    Pahuja DN, DeLuca HF (1981) Stimulation of intestinal calcium transport and bone calcium mobilization by prolactin in vitamin D-deficient rats. Science 214:1058–1039Google Scholar
  21. 21.
    Bloom HJG, Richardson WW (1957) Histological grading and prognosis in breast cancer. A study of 1,409 cases of which 359 have been followed for 15 years. Br J Cancer 11:359–377PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Norio Kohno
    • 1
  • Sohei Kitazawa
    • 2
  • Masaaki Fukase
    • 3
  • Yoko Sakoda
    • 1
  • Yoshihiro Kanbara
    • 1
  • Yoshihiko Furuya
    • 1
  • Osamu Ohashi
    • 1
  • Yoshio Ishikawa
    • 1
  • Yoichi Saitoh
    • 4
  1. 1.The Department of SurgeryHyogo Medical Center for AdultsAkashiJapan
  2. 2.The Second Department of PathologyKobe University School of MedicineKobeJapan
  3. 3.The Third Division of Internal MedicineKobe University School of MedicineKobeJapan
  4. 4.The First Department of SurgeryKobe University School of MedicineKobeJapan

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