Aneeta Patel ¹, Cydney Fenton ^2,4, Raul Ramirez ^2,4, Catherine A. Dinauer ^2,4, R. Michael Tuttle ³, Yuri E. Nikiforov ⁵, and Gary L Francis ^2,4

1 Departments of Clinical Investigation, ² Pediatrics, and ³ Medicine, Walter Reed Army Medical Center, Washington, DC 20307-5001; ⁴ Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD and ⁵ Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Materials and Methods

3.1. Approval
3.2. Patients
3.3. Immunohistochemistry
3.4. Data analysis and statistical comparisons

4. Results

5. Discussion

6. Acknowledgment

7. References

1. ABSTRACT

Tyrosine kinases (TKs) are important candidate genes for malignant transformation and at least 21 different TKs have been identified in the thyroid gland. We hypothesized that the collective activity of these TKs might be increased in thyroid carcinoma and have association with the clinical behavior of individual tumors. To test this, we determined TK expression by immunohistochemistry in 74 archival thyroid tissue blocks (48 papillary thyroid carcinoma, PTC; 9 follicular thyroid carcinoma, FTC; 17 benign thyroid diseases) from children and young adults. Mean TK expression was greater for PTC (2.1 ± 0.11) than benign lesions (1.6 ± 0.2, p = 0.027), and also tended to be greater in FTC (2.1 ± 0.25, p = 0.12). Recurrence risk was three-fold greater for PTC with intense TK expression (4/15, 27%) than for PTC with minimal - moderate TK expression (3/33, 9.0%). However, this was not statistically significant (p = 0.10). In PTC, TK expression correlated with expression of the receptor for hepatocyte growth factor / scatter factor (cMET, r = 0.31, p = 0.044). In FTC, TK expression did not correlate with cMET, but tended to be greater in young patients (r = -0.59, p = 0.09). We conclude that TK expression is increased in PTC and possibly associated with an increased recurrence risk.