Clinical Significance of Histone Deacetylase (HDAC)-1, -2, -4 and -6 Expression in Salivary Gland Tumors

Abstract

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.

Histone Deacetylase (HDAC)-1, -2, -4, and -6 in Uveal Melanomas: Associations with Clinicopathological Parameters and Patients’ Survival

“…In the last decade, HDACs have been suggested to play a crucial role in the regulation of cell proliferation, differentiation, and apoptosis in various human hematological, solid, and mesenchymal malignancies [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. HDAC IHC expression has been described in several tumor types, being associated with important clinicopathological parameters, including patients’ prognosis [ 18 , 19 , 20 , 22 , 24 , 25 , 26 ].…”

“…Red chromogen visualization kit enabled visualization in tissues containing a large amount of melanin. Appropriate negative and positive controls were used as appropriate [ 18 ].…”

Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia

“…A notable amount of research has been performed regarding HDACs' clinical significance in oral cancer and less in nasopharyngeal cancer and salivary gland tumors [12][13][14][15][16][17][18][19][20][21] (Table 2). HDAC-2 was found to be overexpressed in the majority of cases with epithelial dysplasia and oral squamous cell carcinoma (SCC) without, however, showing any noteworthy correlation with sex, age or oral habits in those patients [20].…”

“…Another study performed on a series of nasopharygeal cancer (NPC) cases, revealed a positive association among the increased HDAC-4 levels in primary and metastatic NPC tissues with poor overall survival (OS) and progression-free survival (PFS) [18]. Regarding salivary gland tumors (SGTs), the only clinical associations studied are between the expression of HDAC-1, -2, -4 and -6 in both benign and malignant tumors [19]. More precisely, HDAC-2 upregulation was associated with a better OS and prognosis, while HDAC-6 overexpression revealed to be a negative prognosticator of patients suffering from malignant SGTs [19].…”

“…Regarding salivary gland tumors (SGTs), the only clinical associations studied are between the expression of HDAC-1, -2, -4 and -6 in both benign and malignant tumors [19]. More precisely, HDAC-2 upregulation was associated with a better OS and prognosis, while HDAC-6 overexpression revealed to be a negative prognosticator of patients suffering from malignant SGTs [19]. Furthermore, although staining intensity did not reveal a statistical difference among benign and malignant SGTs, when coupling benign and low-grade malignant SGT cases together, the staining intensity for HDAC-2 and -6 successfully differentiated high-grade malignant tumors from benign and low-grade malignant tumors [19].…”