Dual Immunoistochemical Analysis for MYC and p63 Distinguishes Prognostic Subgroups in Adenoid Cystic Carcinoma

Background: Adenoid cystic carcinoma (ACC) is a rare carcinoma affecting salivary glands and other anatomical sites, including the tracheobronchial tree. Recently, ACCs have been classified into two molecular subtypes through proteogenomic analysis. ACC-I tumors are characterized by MYC hyperactivation and worse prognosis, while ACC-II subgroup is associated with hyperexpression of TP63 and receptor tyrosine kinase (RTKs) genes and by a more indolent clinical course. Previous evidence suggests that immunohistochemistry (IHC) for c-Myc and p63 is sufficient to stratify ACCs of the salivary glands into ACC-I and ACC-II subtypes. Aim of the study: The aim of the present study was to evaluate c-Myc and p63 expression through IHC in ACCs of the lung, which have not been considered in previous studies, and of the salivary glands, in order to determine if the expression of these two markers correlates with histopathological characteristics of the tumors and with prognosis. Materials and methods: We considered 52 cases of ACC, 29 of the salivary glands (SG-ACCs) and 23 of the tracheobronchial tree (TB-ACCs). Formalin-fixed paraffin-embedded (FFPE) tissue samples together with all available hematoxylin and eosin (HE) stained sections and IHC slides were retrieved from the archives of our Institution; complete clinical information was obtained. For each case we performed IHC for c-Myc and p63. We then evaluated the correlation between the expression of these two markers and clinical and pathological variables, such as tumor growth pattern, overall survival (OS) and disease-free survival (DFS). Results: We found that c-Myc was overexpressed in 15 cases (28.85%), 12 SG-ACCs and 3 TB-ACCs, with a significantly higher proportion in tumors of the salivary glands with c-Myc positivity. In our series, c-Myc and p63 expression were negatively correlated. Low p63 expression and c-Myc positivity were correlated with the presence of solid growth pattern. Moreover, solid growth pattern and c-Myc overexpression were significantly associated with reduced OS. Conclusions: The presence of solid growth pattern and the positivity of c-Myc evaluated through IHC in ACCs of the salivary glands and the tracheobronchial tree can provide prognostic information and could help optimize treatment strategies.