title: From nodule to differentiated thyroid carcinoma: contributions of molecular analysis in 2012.
abstract: Today there is a better understanding of the events involved in the initiation and progression of thyroid cancer. It is indeed now known that BRAF and RAS mutations and RET/PTC and PAX8/PPARγ rearrangements account for the majority of molecular alterations detected in differentiated thyroid cancers. Abnormal regulation of microRNAs (miRNAs) is also a promising way of research. The diagnostic utility and prognostic value of detecting these molecular events has been analyzed in several recent studies. BRAF mutation analysis improves the performance of fine-needle aspiration diagnosis by increasing specificity in "indeterminate" cytologies and sensitivity in false negatives. Testing for a "panel of mutations" (BRAF, RAS, RET/PTC and PAX8/PPARγ) improves the performance, detecting papillary carcinomas with non-classic histology. The specificity of these analyzes is excellent but their sensitivity is still insufficient. In the future, specific miRNAs expression profiles in thyroid carcinoma and identification of new mutations might provide interesting information. Several studies have found that BRAF mutations are associated with a more aggressive tumor behavior, a higher risk of recurrence and treatment failure. With regard to the other mutations and rearrangements, current data are conflicting and it seems premature to draw practical conclusions applicable in routine practice. Lastly, targeted therapy with tyrosine kinase inhibitors, based on our understanding of the molecular mechanisms of thyroid oncogenesis, has shown promise in metastatic, progressive, and radioactive iodine-refractory differentiated thyroid carcinomas.
authors.affiliation: Department of Endocrinology, centre de référence des maladies rares d'origine hypophysaire, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille (AP-HM), 13385 Marseille cedex 05, France. frederique.albarel@ap-hm.fr
authors.forename: Frédérique
authors.initials: F
authors.lastname: Albarel
authors.forename: Bernard
authors.initials: B
authors.lastname: Conte-Devolx
authors.forename: Charles
authors.initials: C
authors.lastname: Oliver
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis / Q000379:methods; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000072079:Patched Receptors; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D000072079:Patched Receptors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf