Characteristics of Papillary and Follicular Thyroid Carcinomas with Distant Metastases

Most patients treated for papillary and follicular thyroid cancer have a good prognosis; however, the outcomes are worse once distant metastases are diagnosed. Early detection of distant metastases is important to improve therapeutic outcomes for patients with thyroid cancer. Metastasis of primary thyroid cancer cells to distant tissues proceeds in steps, including intravasation, survival in the blood stream, extravasation, and survival in distant tissues, where the cells colonize and proliferate as a secondary tumor. In this proposal, our goal is to identify clinical and pathophysiological indicators for the presence of distant metastases in patients with papillary and follicular thyroid cancer. Accordingly, we will compare the expression of various tumor markers in primary and metastatic thyroid cancer tissues. In addition, we will analyze for circulating tumor cells (CTCs) in patients in different clinical stages of papillary and follicular thyroid carcinoma. Patients with thyroid cancer and their tissue samples will be selected from the database of the Chang Gung Medical Center in Linkou. There are 2,570 papillary and follicular thyroid cancer patients undergoing regular follow-up. Among them, 146 presented with distant metastases at the time of first thyroidectomy. In another 112 cases, distant metastases developed during the follow-up period. This provides the opportunity to analyze patients with both early and delayed distant metastases. To confirm that the metastatic lesions are of thyroid origin, a small portion of patients underwent tissue biopsy or removal. Primary thyroid tumors and tumors from distant metastatic sites will be obtained from the pathology department for immunohistochemical analysis. The expression of multiple integrin subunits and of pituitary tumor-transforming gene (PTTG)-binding factor (PBF) will be analyzed in sections from formalin-fixed, paraffin-embedded surgical specimens of 20 patients. CTCs in 100 patients with thyroid cancer in different clinical stages will be investigated. CTCs can be enriched from peripheral blood by leukocyte depletion, and we will use a PowerMag system that is designed to enhance leukocyte depletion and CTC detection. We anticipate that the data generated will reveal better prognostic factors for papillary and follicular thyroid carcinomas with distant metastases. Differences in tissue markers between primary and distant metastatic tumors may provide clues as to the mechanism of distant metastases in well-differentiated thyroid cancer. Furthermore, the number of CTCs detected by our method may provide another prognostic indicator for the development of distant metastases.

Project ID:PC10401-0609
External Project ID:MOST103-2314-B182-018-MY3