Reduced chromatin acetylation of malignant salivary gland tumors correlates with enhanced proliferation.
BACKGROUND
Epigenetic changes refer to any heritable modification in gene expression independent of alterations in the DNA sequence. Currently, it is well established that epigenetics represents a crucial player for tumor development. Nevertheless, the epigenetic mechanisms involved in the development and progression of salivary gland tumors (SGTs) remain poorly understood.


METHODS
In this study, we analyzed the pattern of acetyl-histone H3 (lys9) expression in benign and malignant SGTs and further correlate our results with tumors' proliferative activity and clinical outcomes. We assembled tissue microarrays (TMAs) of 84 cases of SGTs and analyzed for acetyl-histone H3 (lys9) and Ki-67 using immunohistochemistry. The study comprised 42 benign and 42 malignant SGTs.


RESULTS
All cases included in this study were positive to acetyl-H3 (lys9). We observed that malignant SGTs were hypoacetylated compared with benign (P = 0.04). Moreover, acetyl-H3 (lys9) expression was inversely correlated with Ki67 (**P = 0.02).


CONCLUSIONS
This study provides the first insight regarding histone modifications in SGTs. Our results suggest that epigenetic mechanism, particularly hypoacetylation of histone H3 (lys9), might play a role in the behavior of salivary gland tumors. Also, our findings suggest that interfering with the acetylation pattern of tumor histones represents a potential novel therapeutic strategy for the treatment of SGTs.
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Department of Experimental Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.|Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Vivian Petersen
VP
Wagner
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Department of Experimental Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.|Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Manoela Domingues
MD
Martins
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Douglas Magno
DM
Guimaraes
Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Department of Experimental Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
Artur Cunha
AC
Vasconcelos
Department of Experimental Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.|Department of Oral Medicine, Hospital de Clínicas de Porto Alegre (HCPA/UFRGS), Porto Alegre, Rio Grande do Sul, RS, Brazil.
Luise
L
Meurer
Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
Pablo Agustin
PA
Vargas
Department of Clinics, Pathology and Surgery, Dental School, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Felipe Paiva
FP
Fonseca
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Cristiane Helena
CH
Squarize
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Rogerio Moraes
http://orcid.org/0000-0001-5358-612X
RM
Castilho
D000107:Acetylation; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology*
D002843:Chromatin
acetylation; epigenetics; head and neck cancer; histone; immunohistochemistry