Calcitonin receptor expression in medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a rare tumor representing 5–10% of thyroid cancers, with a 10-year survival rate is about 50–75%. It arises from a particular thyroid cell type: the parafollicular C-cells of the thyroid which secrete calcitonin (CT). Serum CT is a very sensitive and specific method for diagnosing MTC, however, the potential role of calcitonin receptor (CTR) expression on tumor aggressiveness and prognosis remained to be explored. In order to understand more about the potential role of CTR in MTC, the Cancer Signaling and Metabolism group of I3S/IPATIMUP evaluated CTR expression in a series of MTC and searched for possible associations with clinicopathological, molecular features and prognosis. The results from the present study demonstrated that CTR was expressed in the majority of MTCs. Furthermore, CTR expression was associated with a more differentiated status and clinical and molecular features of good prognosis. Further studies are needed to clarify the function of CTR in normal and tumoral C-cells.

Authors and Affiliations:

Virginia Cappagli^1,2, Catarina Soares Potes^3,4,5, Luciana Bueno Ferreira^1,3,6, Catarina Tavares^1,3,6, Catarina Eloy^1,3, Rossella Elisei², Manuel Sobrinho-Simões^1,3,7,8, Peter J. Wookey⁹, Paula Soares^1,3,6,8

1 Cancer Biology, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal

2 Department of Clinical and Experimental Medicine - Endocrine Section, University of Pisa, Pisa, Italy

3 Cancer Signalling and Metabolism, Instituto de Investigac€a.o e Inovac€a.o em Sau.de - I3S, Porto, Portugal

4 Institute for Molecular and Cell Biology (IBMC), Porto, Portugal

5 Department of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal

6 Department of Pathology and Oncology, Medical Faculty, University of Porto and IPATIMUP, Porto, Portugal

7 Department of Medicine at Austin Health, University of Melbourne, Heidelbeg, Victoria, Australia

Abstract:

Background: Calcitonin expression is a well-established marker for medullary thyroid carcinoma (MTC); yet the role of calcitonin receptor (CTR), its seven-transmembrane G-protein coupled receptor, remains to be established in C-cells derived thyroid tumors. The aim of this work was to investigate CTR expression in MTC and to correlate such expression with clinicopathological features in order to evaluate its possible role as a prognostic indicator of disease aggressiveness and outcome. Methods: Calcitonin receptor expression was analyzed in a series of 75 MTCs by immunohistochemistry, and by qPCR mRNA quantification in specimens from four patients. Statistical tests were used to evaluate the correlation between CTR expression and the clinicopathological and molecular characteristics of patients and tumors. Results: Calcitonin receptor expression was detected in 62 out of 75 samples (82.7%), whereas 13 of the 75 samples (17.3%) were completely negative. CTR expression was significantly associated with expression of cytoplasmatic phosphatase and tensin homologue deleted on chromosome 10 and osteopontin, as well as with wild type RET/RAS genes and absence of tumor stroma, suggesting that CTR expression do not associate with clinicopathological signs of worse prognosis. Discussion: Calcitonin receptor expression appears to be associated in MTC with more differentiated status of the neoplastic cells.

Journal: PeerJ

Link: https://doi.org/10.7717/peerj.3778