ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome.
Genetic predictors of outcome are reviewed in the context of a disease--cancer--that can be (too) simplistically described as a 'successful, invasive clone of our own tissues'. Context has many faces that determine a thyroid cancer patient's outcome beyond the influence of genetic markers. There is also plenty of evidence on the prognostic meaning of the interplay between genetics and context/microenvironment factors (encapsulation, degree of invasion, staging, etc.). This review addresses only genetic alterations detected by molecular methods in surgically resected specimens, thus ruling out immunohistochemistry and (F)ISH, despite their crucial relevance as topographically oriented methods. For the sake of the discussion, well-differentiated carcinomas were divided into two main morphologic types: papillary carcinoma (classic and most variants) displaying BRAFV600E mutations and RET/papillary thyroid carcinoma rearrangements and the group of follicular patterned carcinomas that encompasses follicular carcinoma and the encapsulated form of follicular variant of papillary carcinoma, displaying RAS mutations and PAX8/PPARγ rearrangement. TERT promoter mutations have been recently described (and associated with distant metastases and reduced survival) in papillary and follicular carcinomas, as well as in poorly differentiated and undifferentiated carcinoma. TP53 mutations, previously thought to be restricted to less differentiated carcinomas, were also detected in papillary and follicular carcinoma and found to carry a guarded prognosis. Besides their putative importance for targeted therapies, the prognostic meaning of such mutations is discussed per se and in the setting of concurrent BRAF mutation.
Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and 
Catarina
C
Tavares
Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and 
Miguel
M
Melo
Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal.
José Manuel
JM
Cameselle-Teijeiro
Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and 
Paula
P
Soares
Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias, s/n, 4200-465 Porto, PortugalMedical FacultyUniversity of Porto, Al. Prof. Hernâni Monteiro, P-4200 Porto, PortugalEndocrinologyDiabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, PortugalMedical FacultyUniversity of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalDepartment of PathologyMedical Faculty, Servicio Gallego de Salud-SERGAS, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, SpainDepartment of Pathology and OncologyMedical Faculty of Porto University, Porto, PortugalDepartment of PathologyHospital de S. João, Al. Prof. Hernâni Monteiro, P-4200 Porto, Portugal Instituto de Investigacão e Inovacão em SaúdeUniversidade do Porto, 4200-135 Porto, PortugalCancer BiologyInstitute of Molecular Pathology and 
Manuel
M
Sobrinho-Simões
D014408:Biomarkers, Tumor / Q000235:genetics; D004701:Endocrine Gland Neoplasms / Q000175:diagnosis / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human