Prognostic and Predictive Markers in Medullary Thyroid Carcinoma
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Prognostic and Predictive Markers in Medullary Thyroid Carcinoma Boban M. Erovic & Dae Kim & Clarissa Cassol & David P. Goldstein & Jonathan C. Irish & Sylvia L. Asa & Ozgur Mete Published online: 13 November 2012 # Springer Science+Business Media New York 2012
Abstract Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to adjuvant treatment with radioactive iodine. The clinical management of patients with advanced or metastatic disease remains challenging since no effective systemic adjuvant therapy is available. We aimed to identify markers of aggressive disease and novel drugable protein targets that would provide systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma. We therefore examined morphologic features of aggressive behavior and the expression of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation, cell adhesion, tumorspecific markers, and WNT, SHH, and AKT pathways using tissue microarray from 23 patients with medullary thyroid carcinoma. Protein expression was determined using computerized image analysis software. Statistical analysis was carried out to correlate clinical data with the average score for each marker. Angioinvasion proved to be the most reliable predictor of disease recurrence and death. The rate of angioinvasion was 43 %. All angioinvasive medullary thyroid carcinomas had locoregional and/or distant metastasis; 60 % of angioinvasive medullary thyroid carcinomas developed distant metastasis. We identified expression of several potentially important protein targets such as COX-1/2, Bcl-2a, Gst-π, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be therapeutically targeted in medullary thyroid carcinoma. More importantly, the immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have clinical relevance for the B. M. Erovic : D. Kim : D. P. Goldstein : J. C. Irish Department of Otolaryngology–Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada C. Cassol : S. L. Asa : O. Mete (*) Department of Pathology, University Health Network, 200 Elizabeth Street, 11th Floor, Toronto, ON M5G 2C4, Canada e-mail: [email protected]
administration of peptide receptor radionuclide treatment. Successful outcome of clinical trials directed against these novel targets would provide much needed systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma, and our data suggest the possibility of stratifying patients who are likely to require adjuvant therapy before their burden of disease precludes successful therapeutic effect. Keywords Target proteins . Targeted anticancer therapy . Personalized medicine . Angioinvasion . Peptide receptor radionuclide therapy . Medullary thyroid carcinoma
Introduction Medullary thyroid carcinoma (MTC) is a relatively rare but slow-growing and highly aggressive malignant neoplasm that originates from calcitonin-producing parafollicular C-cells of the thyroid [1, 2]. Although a majority of MTC occurs sporadically, up to 25 % is h
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