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Lack of association between BRAF V600E mutation and mitogen‐activated protein kinase activation in papillary thyroid carcinoma
Author(s) -
Zuo Hui,
Nakamura Yasushi,
Yasuoka Hironao,
Zhang Ping,
Nakamura Misa,
Mori Ichiro,
Miyauchi Akira,
Kakudo Kennichi
Publication year - 2007
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2007.02050.x
Subject(s) - mapk/erk pathway , mutation , cancer research , v600e , thyroid carcinoma , protein kinase a , kinase , biology , microbiology and biotechnology , papillary thyroid cancer , gene , thyroid , genetics
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 0e;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.