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Expression of Transforming Growth Factor ß Type II Receptors in Head and Neck Squamous Cell Carcinoma¹

Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Departments of Biochemistry and Molecular Biology [M. A., T. M-A.], Pathology [C. A. M-C.], and Surgery [J. C.], University of South Florida, Tampa, Florida 33612

Transforming growth factor (TGF)-ß is a potent regulator of growth and differentiation in normal squamous epithelium. TGF-ß exerts its antiproliferative effect via the TGF-ß type II receptor (TßR-II). A decrease in TßR-II expression is believed to be responsible, in part, for the resistance of squamous cell carcinoma (SqCC) to the antiproliferative effects of TGF-ß. In the present study, we used immunohistochemistry and in situ hybridization to analyze the expression of TßR-II along the successive oncogenic stages of head and neck squamous neoplasia, from normal epithelium to dysplasia to carcinoma. Quantitation of TßR-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 TßR-II. In every tumor, the superficial component showed more intense receptor expression than the invasive component. These results indicate that TßR-II expression inversely correlates with disease aggressiveness and suggest that aberrant TßR-II expression is a contributing factor to the pathogenesis of SqCC.

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