Salivary gland tumors (SGTs) comprise a group of rare neoplasms. Locally aggressive, recurrent and/or metastatic SGTs are notorious for their resistance to systemic therapy, making the need for carefully designed, prospective and randomized trials with useful predictive markers mandatory to define new effective therapeutic protocols. Histone Deacetylases (HDACs), are thought to play a crucial role in carcinogenesis. They affect the DNA structure, being also able to regulate its transcription, repair, and replication. This study aimed to evaluate—to our knowledge for the first time—the HDAC-1, -2, -4 and -6 immunohistochemical expression in SGTs and their potential use as prognostic biomarkers. Medical records and archival histopathological material of 58 (36 benign and 22 malignant) SGT patients were included in this study. The H-score was statistically correlated with the clinicopathological characteristics for all cases and patients’ survival rate in malignant SGTs. HDAC-2 positivity was significantly associated with more prolonged overall survival (OS) of patients with malignant SGTs (p = 0.028), while HDAC-2 positivity and no HDAC-6 expression were associated with prolonged OS of patients with HG malignant SGT (p = 0.003 and p = 0.043, respectively). Additionally, a high HDAC-2 H-score was significantly associated with longer OS for HG malignant SGT patients (p = 0.027). In our study, HDAC-2 expression is a marker for good prognosis, whereas HDAC-6 expression indicated poor prognosis; thus, an inhibitor of HDAC-6 may be used to improve patients’ survival.

Salivary gland carcinomas (SGCs) represent a group of rare tumors, with complete surgical resection being the main treatment option. Therapeutic armory for cases of locally aggressive, recurrent, and/or metastatic SGCs, though, remains poor since they exhibit high rates of resistance to systematic therapy. Angiogenesis is considered one of the contemporary hallmarks of cancer and anti-angiogenic factors have already been approved for the treatment of several cancer types. This review aims to summarize, in a histotype-specific manner, the most current available data on the angiogenic factors implicated in SGC angiogenesis, in order to highlight the differences between the most common SGC histotypes and the factors that may have a potential role as therapeutic targets.