Overexpression of the Wilms' tumor gene WT1 in primary thyroid cancer.
The expression levels of the Wilms' tumor gene WT1 were examined in 34 primary thyroid cancers (24 papillary, 5 follicular, 1 anaplastic, and 4 medullary carcinomas), 17 thyroid follicular adenomas, and 6 normal-appearing thyroid tissues using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In 33 of 34 thyroid cancers, the WT1 mRNA was expressed at levels ranging from 5.0 x 10 (-5) to 8.3 x 10 (-2) levels (WT1 expression level in K562 leukemic cells was defined as 1.0). The WT1 mRNA expression levels were significantly higher than those in either thyroid follicular adenomas (P < 0.001) or normal-appearing thyroid tissues (P < 0.01). Immunohistochemical analysis confirmed the expression of WT1 protein in 20 of 21 thyroid cancers with WT1 mRNA expression. WT1 protein was also detected in 6 of 7 follicular adenomas with WT1 mRNA expression. However, the intensity of staining of WT1 protein in adenoma cells was weaker than that in cancer cells and its expression was restricted to approximately 30-80% of adenoma cells in the tumors examined. The direct sequencing analysis of the WT1 genomic DNA showed no mutations in any of the 10 exons of the WT1 gene in all of the 9 different thyroid cancers. These findings indicate an important role of the wild-type WT1 gene in the tumorigenesis of primary thyroid cancer.
Oji
Yusuke
Y
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Miyoshi
Yasuo
Y
Koga
Satoko
S
Nakano
Yoko
Y
Ando
Akiko
A
Nakatsuka
Shin-ichi
S
Ikeba
Ai
A
Takahashi
Eigo
E
Sakaguchi
Nao
N
Yokota
Asumi
A
Hosen
Naoki
N
Ikegame
Kazuhiro
K
Kawakami
Manabu
M
Tsuboi
Akihiro
A
Oka
Yoshihiro
Y
Ogawa
Hiroyasu
H
Aozasa
Katsuyuki
K
Noguchi
Shinzaburo
S
Sugiyama
Haruo
H
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016162:Genes, Wilms Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics
D017931:DNA Primers; D025721:WT1 Proteins