Expression of transforming growth factor beta type II receptors in head and neck squamous cell carcinoma.
Transforming growth factor (TGF)-beta is a potent regulator of growth and differentiation in normal squamous epithelium. TGF-beta exerts its antiproliferative effect via the TGF-beta type II receptor (TbetaR-II). A decrease in TbetaR-II expression is believed to be responsible, in part, for the resistance of squamous cell carcinoma (SqCC) to the anti-proliferative effects of TGF-beta. In the present study, we used immunohistochemistry and in situ hybridization to analyze the expression of TbetaR-II along the successive oncogenic stages of head and neck squamous neoplasia, from normal epithelium to dysplasia to carcinoma. Quantitation of TbetaR-II expression in 38 SqCCs was assessed on a visual scale ranging from negative (absence of staining) to 3+ (strong staining). Normal squamous epithelium and squamous epithelium in the vicinity of the tumors showed homogenous receptor expression with moderate intensity. Dysplastic epithelium and carcinoma in situ showed a mild decrease in receptor expression intensity. Well-differentiated to moderately differentiated carcinomas showed heterogeneous expression of variable intensity, and poorly differentiated carcinomas were completely devoid of TbetaR-II. In every tumor, the superficial component showed more intense receptor expression than the invasive component. These results indicate that TbetaR-II expression inversely correlates with disease aggressiveness and suggest that aberrant TbetaR-II expression is a contributing factor to the pathogenesis of SqCC.
Muro-Cacho
C A
CA
Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Biochemistry and Molecular Biology, University of South Florida, Tampa 33612, USA.
Anderson
M
M
Cordero
J
J
Muñoz-Antonia
T
T
D030201:Activin Receptors, Type I; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II