Expression of transforming growth factor-alpha in adenoid cystic carcinoma of the salivary gland.

BACKGROUND: Transforming growth factor-alpha (TGF-alpha) is expressed in both normal and malignant epithelial cells. Although the expression of TGF-alpha has been extensively studied in some human epithelial neoplasms, its expression in adenoid cystic carcinomas (ACCs) of the salivary gland has not been reported. METHODS: This study used an immunohistochemical technique to assess the expression of TGF-alpha in 40 ACC specimens from the salivary glands, seven specimens from labial minor salivary glands adjacent to mucoceles, and five specimens from normal submandibular glands. RESULTS: In the normal submandibular gland specimens, positive TGF-alpha staining was found in all ductal segments as well as in serous and some mucous acinar cells. In labial minor salivary glands adjacent to mucoceles, positive TGF-alpha staining was found in ductal, serous acinar, serous demilune, and a few mucous acinar cells. Positive TGF-alpha immunostaining was observed in all five salivary gland ACC specimens with a solid histologic pattern, and 31 of the 35 salivary gland ACC specimens with a tubulo-cribriform histologic pattern. Overall, 36 of 40 ACCs of the salivary gland expressed TGF-alpha. Positive TGF-alpha staining was found in the salivary gland ACC specimens with solid, tubular, duct-like, and pseudocystic structures. No significant correlation was found between TGF-alpha expression in ACCs of the salivary gland and age, sex, primary cancer location, TNM status, clinical stage, prognosis, histologic type, perivascular or perineural invasion, focal necrosis of the tumor, or cellular atypia. CONCLUSIONS: This study demonstrated that ductal and acinar cells of the normal submandibular gland and of labial minor salivary glands adjacent to mucoceles are the major sites of TGF-alpha synthesis and secretion. Furthermore, TGF-alpha is biosynthesized in salivary gland ACC tumor cells, forming solid, tubular, duct-like, and pseudocystic structures. Our data suggest that TGF-alpha may play an important biologic role as a mitogen in the growth of salivary gland ACC.