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

Background: Transforming growth factor-alpha (TGF-alpha) is expressed in bo th normal and malignant epithelial cells. Although the expression of TGF-al pha has been extensively studied in some human epithelia] neoplasms, its ex pression in adenoid cystic carcinomas (ACCs) of the salivary gland has not been reported. Methods. This study used an immunohistochemical technique to assess the exp ression of TGF-alpha in 40 ACC specimens from the salivary glands, seven sp ecimens front labial minor salivary glands adjacent to mucoceles, and five specimens from normal submandibular glands. Results: In the normal submandibular gland specimens, positive TGF-alpha st aining was found in all ductal segments as well as in serous and some mucou s acinar cells. In labial minor salivary glands adjacent to mucoceles, posi tive TGF-alpha staining was found in ductal, serous acinar, serous demilune , and a few mucous acinar cells. Positive TGF-alpha immunostaining was obse rved in all five salivary gland ACC specimens with a solid histologic patte rn, 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 s ignificant correlation was found between TGF-alpha expression in ACCs of th e salivary gland and age, sex, primary cancer location, TNM status, clinica l stage, prognosis, histologic type, perivascular or perineural invasion, f ocal necrosis of the tumor, or cellular atypia. Conclusions: This study demonstrated that ductal and acinar cells of the no rmal submandibular gland and of labial minor salivary glands adjacent to mu coceles are the major sites of TGF-alpha synthesis and secretion. Furthermo re, TGF-alpha is biosynthesized in salivary gland ACC tumor cells, forming solid, tubular, duct-like, and pseudocystic structures. Our data suggest th at TGF-alpha may play an important biologic role as a mitogen in the growth of salivary gland ACC.