Transforming growth factor-beta type II receptors and smad proteins in follicular thyroid tumors.
OBJECTIVE
Resistance to transforming growth factor (TGF)-beta-mediated cell growth inhibition is a well-known pathogenic mechanism in epithelial neoplasia. TGF-beta signaling requires normal function of downstream mediators such as TGF-beta receptors (TbetaRs) and Smad proteins. The goal of this study is to investigate the expression of components of the TGF-beta signaling pathway in follicular tumors of the thyroid.


METHODS
Twenty follicular thyroid neoplasms were classified as adenomas (11) or minimally invasive follicular carcinomas (9) according to current pathological criteria. Protein expression was evaluated to identify differences between benign and malignant tumors that could be used as an adjunct to histopathological analysis.


METHODS
Paraffin-embedded tissue sections containing tumor and adjacent nonneoplastic parenchyma were analyzed by immunohistochemistry for the expression of TbetaR type II (TbetaR-II) and Smad2, Smad4, Smad6, and Smad7. Expression of each protein in the tumor was compared with that of the corresponding adjacent nonneoplastic thyroid parenchyma.


RESULTS
TbetaR-II expression was lost in 78% of the carcinomas. In the remaining 22%, TbetaR-II was preserved but Smad2 expression was lost. In all conventional adenomas, however, TbetaR-II expression was maintained. Furthermore, all tumors with normal expression of all proteins were adenomas.


CONCLUSIONS
Downregulation of TbetaR-II is a consistent abnormality in follicular carcinomas and can be used to differentiate minimally invasive carcinomas from adenomas. Also, downregulation of Smad proteins is another mechanism by which carcinomas can become independent from TGF-beta-mediated growth inhibition.
West
J
J
Department of Otolaryngology and Head and Neck Surgery, Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612-9297, USA.
Munoz-Antonia
T
T
Johnson
J G
JG
Klotch
D
D
Muro-Cacho
C A
CA
D018263:Adenocarcinoma, Follicular / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; C497802:SMAD6 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D015534:Trans-Activators