title: High expression of H3K9me3 is a strong predictor of poor survival in patients with salivary adenoid cystic carcinoma.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
authors.affiliation: From the Department of Oral Pathology, 9th People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China (Drs Xia, Tian, Zhang, Wang, Hu, Han, and Li); the Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland (Dr Xia); and the Department of Oral Medicine, Shanghai Stomatological Disease Center, Shanghai, China (Dr Zhou). Ronghui Xia and Rongrui Zhou contributed equally to this work.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Xia
authors.forename: Rongrui
authors.initials: R
authors.lastname: Zhou
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tian
authors.forename: Chunye
authors.initials: C
authors.lastname: Zhang
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D003528:Carcinoma, Adenoid Cystic / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D019175:DNA Methylation; D004273:DNA, Neoplasm; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012468:Salivary Gland Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase