title: Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma.
abstract: BACKGROUND
  Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) 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
  The objective of this study is 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, OPNb and OPNc) in six 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 significantly at 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 MTC-derived cell line (TT).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e In
authors.forename: Luciana Bueno
authors.initials: LB
authors.lastname: Ferreira
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil.
authors.forename: Catarina
authors.initials: C
authors.lastname: Eloy
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil.
authors.forename: Ana
authors.initials: A
authors.lastname: Pestana
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil.
authors.forename: Joana
authors.initials: J
authors.lastname: Lyra
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil.
authors.forename: Margarida
authors.initials: M
authors.lastname: Moura
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e In
authors.forename: Hugo
authors.initials: H
authors.lastname: Prazeres
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e In
authors.forename: Catarina
authors.initials: C
authors.lastname: Tavares
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e In
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil.
authors.forename: Etel
authors.initials: E
authors.lastname: Gimba
authors.affiliation: Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (Ipatimup) - Cancer BiologyRua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalUnidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Professor Lima Basto, 1099-023 Lisboa, PortugalMolecular Pathology Service of the Portuguese Institute of Oncology of Coimbra FGEPE, Avenue. Bissaya Barreto, 98, 3000-075 Coimbra, PortugalDepartment of PathologyHospital de S. João, Al. Professor Hernâni Monteiro, P-4200 Porto, PortugalResearch CoordinationNational Institute of Cancer, Rio de Janeiro 22743-051, BrazilNatural Sciences DepartmentHealth and Humanities Institute, Fluminense Federal University, Rio das Ostras, Rio de Janeiro 28895-532, Brazil Instituto de Investigação e In
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D053495:Osteopontin