|Department Affiliations||Chief Endocrine Surgery Department of Surgery Co-Director of Basic and Translational Research|
|SOM Address||606 Blalock|
Although thyroid cancer is one of the fastest growing cancers in the United States, the incidence having doubled in the last decade (http://seer.cancer.gov), it is well known that cytopathologists often experience difficulties in preoperatively diagnosing thyroid lesions as either benign or malignant. As a result, 20-25% of fine needle aspirates (FNA) are reported as indeterminate, and 10-15% as inadequate for diagnosis. Thus, there are over 100,000 patients a year who present in the United States with indeterminate thyroid neoplasms. Because the clinician and surgeon cannot determine malignancy pre- or intra-operatively, patients with indeterminate thyroid lesions on FNA cannot be optimally clinically managed. Therefore, additional diagnostic markers of malignancy are greatly needed. We know from review of the Johns Hopkins experience over the last 10 years  that thyroid tumors posing a diagnostic dilemma for the clinician include 8 different histopathological subtypes; papillary thyroid cancer, follicular variant of papillary thyroid cancer, follicular cancer, Hürthle cell cancer, adenomatoid nodule, follicular adenoma, Hürthle cell adenoma, and lymphocytic thyroiditis nodule. All eight of these different tumor types therefore require the identification of distinguishing diagnostic markers. Our laboratory currently is investigating this problem utilizing 3 main approaches: 1) we are in the process of validating genes, identified by oligonucleotide microarray analysis as differentiating between benign and malignant tumors [2, 3] using RT-PCR and immunocytochemistry on thyroid FNA samples; 2) we are also validating potential splice variant patterns identified by splice array analysis that may be useful in differentiating the tumors. As a prototype to the latter approach we have documented differentiating splice variant patterns of hTERT in thyroid tumor samples  and plan to develop a more comprehensive panel of splice patterns useful in differential diagnosis; and 3) our statisticians are working to develop novel approaches to the high-dimensional data that our laboratory generates . Our laboratory is involved in the entire process of “bench to bedside research”, enrolling patients with thyroid tumors in clinical protocols, collecting thyroid specimens, performing molecular biologic assays on these specimens, followed by validating our laboratory findings on FNA specimens. Our goal in the near future is to directly apply our results to the management of patients with indeterminate thyroid tumors.
- Banks, N.D., et al., A diagnostic predictor model for indeterminate or suspicious thyroid FNA samples. Thyroid, 2008. 18(9): p. 933-41.
- Prasad, N.B., et al., Identification of genes differentially expressed in benign versus malignant thyroid tumors. Clin Cancer Res, 2008. 14(11): p. 3327-37.
- Mazzanti, C., et al., Using gene expression profiling to differentiate benign versus malignant thyroid tumors. Cancer Res, 2004. 64(8): p. 2898-903.
- Wang, Y., et al., Differentiating alternative splice variant patterns of human telomerase reverse transcriptase in thyroid neoplasms. Thyroid, 2008. 18(10): p. 1055-63.
- Kowalski, J., Talbot, C., Tsai, HL, Prasad, N., Umbricht, C., Zeiger, M., From Ambiguities to Insights in Cancer Diagnosis via Query-based Comparisons. J of Pattern Recognition (in press).