Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and malignant thyroid lesions

J Pathol. 2002 Oct;198(2):157-62. doi: 10.1002/path.1185.


Cyclin D1 and E2F-1 proteins are essential for the regulation of the G1/S transition through the cell cycle. Cyclin D1, a product of the bcl-1 gene, phosphorylates the retinoblastoma protein, releasing E2F-1, which in turn activates genes involved in DNA synthesis. Expression patterns of E2F-1 protein in thyroid proliferations have not been reported. This study used monoclonal antibodies for cyclin D1 and E2F-1 proteins to immunostain sections of normal thyroid, hyperplastic (cellular) nodules, follicular adenomas, follicular carcinomas, and papillary carcinomas. The proliferation rate was examined using an antibody specific for the Ki-67 antigen. Fluorescence in situ hybridization (FISH) methods and chromosome 11-specific probes were also employed to determine chromosome copy number and to assess for evidence of amplification at the 11q13 locus in papillary and follicular carcinomas with cyclin D1 overexpression. Concurrent overexpression of Ki-67, cyclin D1, and E2F-1 was found in the majority of benign and malignant thyroid lesions, compared with normal thyroid tissue. Cyclin D1 up-regulation was not due to extra copies of chromosome 11, or bcl-1 gene amplification. Malignant tumours showed the highest expression for all three markers, particularly papillary carcinomas. E2F-1 was detected at the same or slightly lower levels than cyclin D1. It was only found when cyclin D1 was overexpressed. Because cyclin D1 normally activates E2F-1, up-regulation of cyclin D1 may lead to E2F-1 overexpression in benign and malignant thyroid lesions.

MeSH terms

  • Adenocarcinoma, Follicular / metabolism
  • Adenocarcinoma, Follicular / pathology
  • Adenoma / metabolism
  • Adenoma / pathology
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology
  • Cell Cycle Proteins / metabolism*
  • Cell Division
  • Cyclin D1 / metabolism
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Humans
  • Hyperplasia / metabolism
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / metabolism
  • Neoplasm Proteins / metabolism*
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Transcription Factors / metabolism


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Transcription Factors
  • Cyclin D1