Authors: Juanita J. Evans, Henry S. Crist, Saima Durvesh, Richard D. Bruggeman and David Goldenberg

Juanita J. Evans

Department of Pathology; Penn State Milton S. Hershey Medical Center; Hershey, PA USA

Henry S. Crist

Department of Pathology; Penn State Milton S. Hershey Medical Center; Hershey, PA USA

Saima Durvesh

Division of Endocrinology, Diabetes and Metabolism; Department of Medicine; Penn State Milton S. Hershey Medical Center; Hershey, PA USA

Richard D. Bruggeman

Department of Pathology; Penn State Milton S. Hershey Medical Center; Hershey, PA USA

David Goldenberg

Division of Otolaryngology-Head and Neck Surgery; Penn State Milton S. Hershey Medical Center; Hershey, PA USA

Abstract:
Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and K_i-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p < 0.05) in thyroglobulin expression and statistically significant increases (p < 0.05) in K_i-67 and p53 expression as compared with the PTC cohort. A trend toward loss of p16 and p21 expression was noted in the ATC cohort. A trend toward decreased survival was noted with p21 expression. These data indicate disruption of the normal cell cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

Received: February 15, 2012; Accepted: April 29, 2012; Published Online: June 12, 2012

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