Cell Type-dependent Biomarker Expression in Adenoid Cystic Carcinoma: Biologic and Therapeutic Implications

Background: Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic, and clinical heterogeneity. The authors of this report hypothesized that the dual cellular composition of ACC plays an important role in biomarker evaluation, tumor biologic behavior, and response to therapy.

Methods: To investigate the differential localization and expression of the c-Kit protein and the epidermal growth factor receptor (EGFR) protein, immunohistochemical analyses were performed on tissue arrays that were constructed from 199 tumors, and the results were correlated with clinicopathologic factors.

Results: c-Kit expression was limited to the inner ductal epithelial cells, whereas EGFR expression was limited mainly to the outer myoepithelial cells in the majority of ACCs with tubular and cribriform patterns. In solid ACCs, c-Kit uniformly was positive, whereas EGFR consistently was negative. A significant statistical correlation was observed between c-Kit expression and a poor 3-year outcome, and EGFR expression was correlated with a better 3-year outcome.

Conclusions: The current findings underscored the importance of cellular subtype localization of biomarkers in the clinical and therapeutic stratification of patients with ACC.