High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma

Abstract

Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.

Distant Metastases in Patients with Carcinoma of the Major Salivary Glands

“…For example, the specific genetic features of a cancer in an individual also may have prognostic value. A higher expression of H3K9me3 is correlated with an increased probability of DM ( p = 0.001) in adenoid cystic carcinoma, 13 but also, a higher expression of TMPRSS4 was associated with a higher tendency toward both lymph node metastasis ( p = 0.002) and distant metastasis in ( p < 0.001) in adenoid cystic carcinoma. 14 In one study of salivary duct cancer, p53 expression correlated with local disease recurrence ( p < 0.013), distant metastasis ( p < 0.049), and 5-year survival ( p < 0.008), and HER-2/ neu overexpression correlated with both distant metastasis ( p < 0.034) and 5-year survival ( p < 0.0239).…”

Low expression of endothelin receptor B (EDNRB) is related to H3K9me3 binding with the EDNRB promoter region and is associated with the clinical T tumor stage in salivary adenoid cystic carcinoma

“…21,22 Our previous studies also showed that molecular markers such as H3K9me3 expression can be used as indicators for predicting the prognosis for ACC patients. 15 However, it was not clear which genes were regulated by H3K9me3 to influence tumor characteristics. Building on the results of previous studies, this study further analyzed whether H3K9me3 influenced the biologic behavior of ACC tumors through the silencing of tumor suppressor genes.…”

Clinical impact of 18F‐FDG positron emission tomography/CT on adenoid cystic carcinoma of the head and neck

“…It remains difficult for clinicians to select appropriate treatment strategies and make prognoses for these patients. Many additional clinicopathologic and biologic markers have been investigated for predicting outcomes and supplementing the TNM classifications …”

“…Many additional clinicopathologic and biologic markers have been investigated for predicting outcomes and supplementing the TNM classifications. [4][5][6][7] The 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT provides useful functional and anatomic information and plays a major role in the management of patients affected by head and neck cancer. 8 It is indicated for staging, especially to evaluate lymph nodes and distant metastases involvement in stage III and IV disease, to discriminate between unilateral and bilateral lymph node involvement, and to detect synchronous primaries, with consequent impact on treatment selection in a significant number of patients.…”