Cell cycle regulators show diagnostic and prognostic utility for differentiated thyroid cancer

Ann Surg Oncol. 2007 Dec;14(12):3403-11. doi: 10.1245/s10434-007-9572-8. Epub 2007 Sep 20.


Background: Differentiated thyroid cancer (DTC) generally has a favorable outcome, but some patients develop local recurrence and/or distant metastases and ultimately die of their disease. Molecular markers that accurately predict tumor behavior are lacking. This study's aim was to ascertain the role of cell cycle regulators in predicting malignant histology and tumor behavior in DTC.

Methods: Tissue microarrays consisting of 100 benign and 105 malignant thyroid lesions, plus 24 lymph node samples, were stained for p16, p21, p27, p53, p57, p63, cyclin D1, cyclin E, and mdm2. Statistical analysis was used to compare the expression of the markers in benign versus DTC lesions and correlate their expression with clinicopathologic characteristics.

Results: p16, p21, cyclin D1, and cyclin E showed significantly (P < .001) increased expression in DTCs compared with benign thyroid lesions (54.7% vs. 5%, 71.7% vs. 38%, 87.1% vs. 45.7%, and 72.3% vs. 37.4%, respectively). There was no significant difference in expression between benign lesions and DTC for the remaining markers. p16 expression correlated significantly with extrathyroidal tumor extension (P = .02) and the presence of cancer in lymph nodes (P = .03). A total of 73% vs. 45% of the cancers of patients with and without lymph node involvement, respectively, stained positive for p16 (P = .01).

Conclusions: There is a statistically significant difference in the expression of p16, p21, cyclin D1, and cyclin E between DTCs and benign thyroid lesions, and p16 expression correlates with clinicopathologic variables predicting poor outcomes for DTC. These results suggest that evaluation of cell cycle derangement in thyroid tumors may serve as a useful tool for both DTC diagnosis and prognosis.

MeSH terms

  • Adenoma / metabolism
  • Adenoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation*
  • Cyclin D1 / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Cyclins / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis / pathology
  • Male
  • Medical Records
  • Middle Aged
  • Oxyphil Cells / pathology
  • Prognosis
  • Prospective Studies
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Tissue Array Analysis
  • Tissue Fixation
  • Tumor Suppressor Proteins / metabolism


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27