title: Lack of association between BRAF V600E mutation and mitogen-activated protein kinase activation in papillary thyroid carcinoma.
abstract: The BRAF V600E mutation has been identified in a high proportion of papillary thyroid carcinoma (PTC). In cell lines and a transgenic mouse model it has been demonstrated that the mutation constitutively activates the mitogen-activated protein kinase (MAPK) pathway but in human PTC samples its effects remain unexamined. Herein the correlation of BRAF mutation and MAPK activation was examined in 42 human PTC samples. Activating mutations of the BRAF gene and all three RAS genes were detected by polymerase chain reaction-direct sequencing, and RET/PTC1 rearrangements were screened by nested reverse transcription-polymerase chain reaction. MAPK activation was assessed by immunohistochemistry and western blot analysis. Twenty-eight cases (66.7%) of BRAF V600E mutation, three cases (7.1%) of RET/PTC1 rearrangement but no cases of RAS genes mutation were identified. Activated MAPK was found in six cases (14.3%) with only two cases of mutant BRAF. In total 7.1% of PTC with BRAF mutation had activated MAPK. Furthermore, BRAF mutations were more prevalent in patients > or =45 years, but did not correlate with aggressive clinical behaviors. Absence of association between BRAF mutation and activation of MAPK pathway in PTC suggests the presence of mechanisms that downregulate MAPK activation.
authors.affiliation: Department of Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hui
authors.initials: H
authors.lastname: Zuo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hironao
authors.initials: H
authors.lastname: Yasuoka
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Misa
authors.initials: M
authors.lastname: Nakamura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Kennichi
authors.initials: K
authors.lastname: Kakudo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases