Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma

Osteopontin (OPN) is a multifunctional protein frequently overexpressed, and involved in tumour progression in different types of cancer. In this study, we found that OPN is expressed in medullary thyroid carcinoma (MTC), C cell hyperplasia and C cells, and at variance with other cancers, OPN expression is associated with good prognostic features and cell differentiation. 

Authors and Affiliations:

Luciana Bueno Ferreira^1,2,3, Catarina Eloy², Ana Pestana², Joana Lyra², Margarida Moura⁴, Hugo Prazeres^1,2,5, Catarina Tavares^1,2,3, Manuel Sobrinho-Simões^1,2,3,6 , Etel Gimba^7,8, Paula Soares^1,2,3

¹Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal;

²Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) – Cancer Biology, Rua Dr. Roberto Frias,
 s/n, 4200-465 Porto, Portugal,

³Medical Faculty, University of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal,

⁴Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal,

⁵Molecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FG, EPE, Av. Bissaya Barreto, 98, 3000-075 Coimbra, Portugal, ⁶Department of Pathology, Hospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal,

⁷Research Coordination, National Institute of Cancer, Rio de Janeiro 22743-051, Brazil,

⁸Natural Sciences Department, Health and Humanities Institute, Fluminense Federal University,
 Rio das Ostras, Rio de Janeiro 28895-532, Brazil.

Abstract:  

Background: Osteopontin (OPN) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C-cell derived thyroid lesions and tumours remains to be established.

Objective: To clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC).

Methods: OPN expression was analysed in a series of 116 MTCs by immunohistochemistry, and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, b and c) in 6 cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours.

Results: OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed at significantly higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the medullary thyroid carcinoma-derived cell line TT.  

Conclusion: The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC.

Journal: European Journal of Endocrinology

Link: http://www.eje-online.org/content/early/2016/01/25/EJE-15-0577