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Cell Cycle Regulators Show Diagnostic and Prognostic Utility for Differentiated Thyroid Cancer

¹ Department of Surgery, St. Paul’s Hospital, University of British Columbia, C303-1081 Burrard Street, V6Z 1Y6, Vancouver, BC, Canada
² Department of Pathology, St. Paul’s Hospital, University of British Columbia, C303-1081 Burrard Street, V6Z 1Y6, Vancouver, BC, Canada
³ Genetic Pathology Evaluation Center at the, Prostate Research Center of Vancouver General Hospital, British Columbia Cancer Agency, and University of British Columbia, Vancouver, BC, Canada
⁴ Department of Medical Genetics, University of British Columbia, British Columbia Cancer Agency, and Michael Smith Genome Sciences Center, Vancouver, BC, Canada
⁵ Department of Medicine, St. Paul’s Hospital, University of British Columbia, C303-1081 Burrard Street, V6Z 1Y6, Vancouver, BC, Canada

Correspondence: Address correspondence and reprint requests to: Sam M. Wiseman, MD, FRCSC; E-mail: smwiseman{at}providencehealth.bc.ca

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.

Key Words: Thyroid cancer • Cell cycle regulators • Tissue microarray

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