Integrating molecular classification in adenoid cystic carcinoma of the head and neck: The experience from four tertiary centers in Greece

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BACKGROUND: Recently, a molecular characterization of adenoid cystic carcinoma (ACC) has been proposed, based on upregulation of c-Myc, a proto-oncogene involved in carcinogenesis, and p63, a transcription factor of the p53 gene family. The aim of this study was to evaluate c-Myc and p63 expression and classify patients with ACC into the proposed molecular groups. METHODS: We included in the analysis 50 patients with ACC of the head and neck region diagnosed treated between 2000 and 2021 in four tertiary referral centers in Greece. Patient demographics and disease characteristics were retrieved from patients' medical records. C-Myc and p63 expression were evaluated by immunohistochemistry. RESULTS: Forty-seven patients were eligible for classification. The majority of patients had primary non-metastatic tumors. P63 protein was found to be overexpressed in 39 patients (78 %), who were classified as ACC type II (ACC-II). Eight patients with no p63 overexpression were classified as ACC type I (ACC-I). Among ACC-II patients, 31 had negative expression of c-Myc and 8 patients had low c-Myc expression. We found a statistically significant difference in the primary tumor location between the two groups (p = 0.0470). Notably, patients that belonged to the ACC-II subgroup had more favorable prognosis (50 months for ACC-I vs. 135 months for ACC-II, p = 0.0066). CONCLUSIONS: We confirmed the recently published data regarding the c-myc/p63 prognostic classification for ACC. Evaluation of c-Myc and p63 should be routinely performed in ACC tumors to allow for accurate stratification and implementation of ACC subtyping for clinical trials.

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