Endocrine Pathology

, Volume 6, Issue 4, pp 279–287 | Cite as

Immunohistochemical analysis of the cell cycle-associated antigens Ki-67 and retinoblastoma protein in parathyroid carcinomas and adenomas

  • Ricardo V. Lloyd
  • J. Aidan Carney
  • Jorge A. Ferreiro
  • Long Jin
  • Geoffrey B. Thompson
  • Jon A. van Heerden
  • Clive S. Grant
  • Peter C. Wollan
Clinical Research

Abstract

The morphologic distinction between parathyroid carcinoma and adenoma can be a difficult diagnostic problem. We analyzed nuclear immunoreactivity for the cell cycle-associated antigen Ki-67 with monoclonal antibody (MAb) MIB-1 and for retinoblastoma (RB) protein with two polyclonal antisera in 24 parathyroid carcinomas and 35 adenomas, which were formalin fixed and paraffin embedded to determine if these antibodies could assist in distinguishing between carcinomas and adenomas. In addition, 10 cases of parathyroid hyperplasia and 5 cases of normal parathyroids were examined as control tissues. The Ki-67 labeling index was significantly higher in parathyroid carcinomas compared to adenomas (7.1 ± 1.0% vs 2.4 ± 0.2%,p<0.001). No patient with a parathyroid adenoma, parathyroid hyperplasia, or normal parathyroid gland had a Ki-67 labeling index >5.3%. Analysis of the primary tumors from patients with recurrent carcinomas and from those with nonrecurrent carcinomas showed a higher mean Ki-67 labeling index (7.8 ± 1.5% vs 5.2 ± 1.1%), in the former group, although these differences were not statistically significant. The RB protein immunoreactivity was not useful in distinguishing between parathyroid carcinomas and adenomas in paraffin-tissue sections.

These results indicate that nuclear immunoreactivity for the cell cycle-associated antigen Ki-67 may be another useful method to assist in distinguishing parathyroid carcinomas from adenomas.

Key Words

Parathyroid Ki-67 retinoblastoma carcinoma adenoma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer 31:600–605, 1973.PubMedCrossRefGoogle Scholar
  2. 2.
    Bondeson L, Sandelin K, Grimelius L. Histopathological variables and DNA cytometry in parathyroid carcinoma. Am J Surg Pathol 17:820–829, 1993.PubMedCrossRefGoogle Scholar
  3. 3.
    Holmes EC, Morten DL, Ketcham AS. Parathyroid carcinoma. A collective review. Am Surg 169:631–640, 1969.Google Scholar
  4. 4.
    Shane E, Bilezikian JP. Parathyroid carcinoma: a review of 62 patients. Endocr Rev 3:218–226, 1982.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang C, Gaz RD. Natural history of parathyroid carcinoma: diagnosis, treatment, and results. Am J Surg 149:522–527, 1985.PubMedCrossRefGoogle Scholar
  6. 6.
    Sandelin K, Auer G, Bondeson L, Gremelius L, Farnebo L-O. Prognostic factors in parathyroid cancer: a review of 95 cases. World J Surg 16:724–731, 1992.PubMedCrossRefGoogle Scholar
  7. 7.
    Wynne AG, van Heerden J, Carney JA, Fitzpatrick LA. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine 71:197–205, 1992.PubMedCrossRefGoogle Scholar
  8. 8.
    Levin KE, Galante M, Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery 101:649–660, 1987.PubMedGoogle Scholar
  9. 9.
    Kay S, Hume DM. Carcinoma of the parathyroid gland: how reliable are the clinical and histologic features? Arch Pathol 96: 316–319, 1973.PubMedGoogle Scholar
  10. 10.
    Gerdes J, Leuke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715, 1984.PubMedGoogle Scholar
  11. 11.
    Cattoretti G, Becker MHG, Key G, et al. Monoclonal antibody against recurrent parts of the Ki-67 antigen (MIB 1 and MIB 3) defect proliferating cells in immune-processed formalin-fixed paraffin sections. J Pathol 168:357–363, 1992.PubMedCrossRefGoogle Scholar
  12. 12.
    Goldblum JR, Shannon R, Kaldjian EP, Thiny M, Davenport R, Thompson N, Lloyd RV. Immunohistochemical assessment of proliferative activity in adenocritical neoplasms. Mod Pathol 6:663–668, 1993.PubMedGoogle Scholar
  13. 13.
    Carr K, Heffess C, Jin L, Lloyd RV. Immunohistochemical analysis of thyroid carcinomas utilizing antibodies to p53 and Ki-67. Appl Immunohistochem 1:201–207, 1993.Google Scholar
  14. 14.
    Abbona GC, Papotti M, Gasparri G, Bussoloti G. Proliferative activity in parathyroid tumors as detected by Ki-67 immunostaining. Human Pathol 26:135–138, 1995.CrossRefGoogle Scholar
  15. 15.
    Dowdy SF, Hinds PW, Louie K., Reed SI, Arnold A, Weinberg RA. Physical interaction of the retinoblastoma protein with human D cyclin. Cell 73:499–511, 1993.PubMedCrossRefGoogle Scholar
  16. 16.
    Benedict WF, Xu H-J, Hu S-X, Takahashi R. Role of the retinoblastoma gene in the initiation and progression of human cancer. J Clin Invest 85:988–993, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Xu H-J, Hu S-X, Benedict WF. Lack of nuclear RB protein staining in Go/middle G1 cells: correlation to changes in total RB protein level. Oncogene 6:1139–1146, 1991.PubMedGoogle Scholar
  18. 18.
    Cryns VL, Thor A, Xu H-J, Hu S-X, Wierman ME, Vickery AL Jr, Benedict WF, Arnold A. Loss of retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med 330:757–761, 1994.PubMedCrossRefGoogle Scholar
  19. 19.
    DeLellis RA. Tumors of the parathyroid gland. Atlas of tumor pathology. 3rd ser. fasicle. Washington, DC: Armed Forces Institute of Pathology, 1993.Google Scholar
  20. 20.
    Loda M, Lipman J, Cukor B, Bur M, Kwan P, DeLellis RA. Nodular foci in parathyroid adenomas and hyperplasias: an immunohistochemical analysis of proliferative activity. Hum Pathol 25:1050–1056, 1994.PubMedCrossRefGoogle Scholar
  21. 21.
    Skalova A, Leivo I, van Buguslawsky K, Saksela E. Cell proliferation correlates with prognosis in acinic cell carcinomas of salivary gland origin. Immunohistochemical study of 30 cases using the MIB1 antibody in formalin-fixed paraffin sections. J Pathol 173:13–21, 1994.PubMedCrossRefGoogle Scholar
  22. 22.
    Böker DK, Stark HJ. The proliferation rate of intracranial tumors as defined by the monoclonal antibody Ki-67. Application of this method to paraffin-embedded specimens. Neurosurg Rev 11:267–272, 1988.PubMedCrossRefGoogle Scholar
  23. 23.
    Hall PA, Richards MA, Gregory WM, d'Ardenne AJ, Lister TA, Stansfeld AG. The prognostic value of Ki-67 immunostaining in non-Hodgkin's lymphoma. J Pathol 154:223–235, 1988.PubMedCrossRefGoogle Scholar
  24. 24.
    Mulder AH, van Hootegem JC, ten Kate FJ, Kurth KH, Ooms EC, Vander Kwast TH, Sylvester R. Prognostic factors in bladder carcinoma: histologic parameters and expression of a cell cycle-related nuclear antigen (Ki-67). J Pathol 166:37–43, 1992.PubMedCrossRefGoogle Scholar
  25. 25.
    Ueda T, Aozasa K, Tsujimoto M, Ohsawa M, Uchida A, Aoki Y, Ono K, Matsumoto K. Prognostic significance of Ki-67 reactivity in soft tissue sarcomas. Cancer 63:1607–1611, 1989.PubMedCrossRefGoogle Scholar
  26. 26.
    Xu H-J, Hu S-X, Cagle PT, Moore GE, Benedict WF. Absence of retinoblastoma protein in primary non-small cell lung carcinomas. Cancer Res 51:2730–2739, 1991.Google Scholar
  27. 27.
    Gilliland DG, Black PM. Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus. J Clin Endocrinol Metab 78:922–927, 1994.PubMedCrossRefGoogle Scholar
  28. 28.
    Kornblau SM, Chen N, del Giglio A, O'Brien S, Deisseroth AB. Retinoblastoma protein expression is frequently altered in chronic lymphocytic leukemia. Cancer Res 54:242–246, 1994.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 1995

Authors and Affiliations

  • Ricardo V. Lloyd
    • 1
    • 2
    • 3
  • J. Aidan Carney
    • 1
    • 2
    • 3
  • Jorge A. Ferreiro
    • 1
    • 2
    • 3
  • Long Jin
    • 1
    • 2
    • 3
  • Geoffrey B. Thompson
    • 1
    • 2
    • 3
  • Jon A. van Heerden
    • 1
    • 2
    • 3
  • Clive S. Grant
    • 1
    • 2
    • 3
  • Peter C. Wollan
    • 1
    • 2
    • 3
  1. 1.Department of Laboratory Medicine and PathologyMayo Clinic and Mayo FoundationRochester
  2. 2.Department of SurgeryMayo Clinic and Mayo FoundationRochester
  3. 3.Department of Biostatistics, Mayo ClinicMayo Clinic and Mayo FoundationRochester

Personalised recommendations