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.
Similar content being viewed by others
References
Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer 31:600–605, 1973.
Bondeson L, Sandelin K, Grimelius L. Histopathological variables and DNA cytometry in parathyroid carcinoma. Am J Surg Pathol 17:820–829, 1993.
Holmes EC, Morten DL, Ketcham AS. Parathyroid carcinoma. A collective review. Am Surg 169:631–640, 1969.
Shane E, Bilezikian JP. Parathyroid carcinoma: a review of 62 patients. Endocr Rev 3:218–226, 1982.
Wang C, Gaz RD. Natural history of parathyroid carcinoma: diagnosis, treatment, and results. Am J Surg 149:522–527, 1985.
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.
Wynne AG, van Heerden J, Carney JA, Fitzpatrick LA. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine 71:197–205, 1992.
Levin KE, Galante M, Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery 101:649–660, 1987.
Kay S, Hume DM. Carcinoma of the parathyroid gland: how reliable are the clinical and histologic features? Arch Pathol 96: 316–319, 1973.
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.
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.
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.
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.
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.
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.
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.
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.
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.
DeLellis RA. Tumors of the parathyroid gland. Atlas of tumor pathology. 3rd ser. fasicle. Washington, DC: Armed Forces Institute of Pathology, 1993.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lloyd, R.V., Carney, J.A., Ferreiro, J.A. et al. Immunohistochemical analysis of the cell cycle-associated antigens Ki-67 and retinoblastoma protein in parathyroid carcinomas and adenomas. Endocr Pathol 6, 279–287 (1995). https://doi.org/10.1007/BF02738728
Issue Date:
DOI: https://doi.org/10.1007/BF02738728