Association between decreased WWOX protein expression and thyroid cancer development.
BACKGROUND
Chromosomal fragile sites are often related to cancer development. The WW domain-containing oxidoreductase gene (WWOX) spans the second most common chromosomal fragile site (FRA16D) and encodes an important proapoptotic protein.


OBJECTIVE
To verify our hypothesis that underexpression of WWOX could contribute to malignant transformation of the thyroid cells.


METHODS
We compared WWOX expression among follicular adenomas (FAs) and differentiated thyroid carcinomas [follicular thyroid carcinomas (FTCs) and papillary thyroid carcinomas (PTCs)] in 53 thyroid tumors resected from patients submitted to total thyroidectomy.


METHODS
Multiple fields of tumor areas of FAs, FTCs, and PTCs as well as normal thyroid tissue were stained with WWOX antiserum, and classified by the extent of staining (percentage of cells staining) and staining intensity.


RESULTS
PTCs showed a significantly decreased expression of WWOX when compared to FAs and FTCs. Further, using a unique model of comparison in patients in whom FAs and PTCs were concomitantly present, we detected the same result (i.e., no expression in PTCs).


CONCLUSIONS
We conclude that WWOX underexpression is an important step that might increase the vulnerability to the carcinogenesis process in PTCs.
Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. epdias@gmail.com
Eduardo P
EP
Dias
Flavio J
FJ
Pimenta
Marta S
MS
Sarquis
Marco A
MA
Dias Filho
C M
CM
Aldaz
Julienne B
JB
Fujii
Ricardo S
RS
Gomez
Luiz
L
De Marco
D018263:Adenocarcinoma, Follicular / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D043283:Chromosome Fragile Sites / Q000502:physiology; D006801:Humans; D010088:Oxidoreductases / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D000074584:WW Domain-Containing Oxidoreductase
D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human