Immunohistochemical and sequencing analyses of the Wnt signaling components in Japanese anaplastic thyroid cancers.
We investigated the status of the components and target genes of the Wnt signaling pathway in Japanese anaplastic thyroid cancers (ATCs) in the present study. Nuclear and cytoplasmic positive staining of beta-catenin, which might indicate the existence of alterations in the Wnt signaling pathway, were found in 40.9% and 63.6% of the 22 ATC samples, respectively. The beta-catenin, adenomatous polyposis coli (APC) and Axin 1 gene mutations were observed in 4.5%, 9.0%, and 81.8% of the 22 ATC samples, respectively. Overexpression of cyclin D1 and c-myc, which are the target genes of the Wnt signaling pathway, was observed in 27.3% and 59.1% of the ATC samples, respectively. There was no significant correlation between nuclear or cytoplasmic positive staining of beta-catenin and nuclear positive staining of cyclin D1 or c-myc. Taken together, the results of beta-catenin immunohistochemistry suggest that alterations in the Wnt signaling pathway are associated with carcinogenesis of ATC, but the frequency of beta-catenin gene mutation in our series is lower than that previously reported. Furthermore, cyclin D1 and c-myc frequently accumulated in ATC, independently of dysfunction in the Wnt signaling pathway.
Kurihara
Takeshi
T
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ikeda
Satoshi
S
Ishizaki
Yasuyo
Y
Fujimori
Masahiko
M
Tokumoto
Noriaki
N
Hirata
Yuzoh
Y
Ozaki
Shinji
S
Okajima
Masazumi
M
Sugino
Keizo
K
Asahara
Toshimasa
T
D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D060466:Axin Protein; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D015534:Trans-Activators / Q000378:metabolism; D051153:Wnt Proteins; D051176:beta Catenin
C555451:AXIN1 protein, human; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1