Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers.

Abstract

DNA methyltransferase 1, 3a, and 3b affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers. The current study was designed to analyze DNA methyltransferase expression by immunohistochemistry in a series of 94 Tunisian sporadic breast carcinomas. Results were correlated to clinicopathologic parameters and promoter methylation status of 8 tumor suppressor genes (BRCA1, BRCA2, RASSFA1, TIMP3, CDH1, P16, RARβ2, and DAPK). Overexpression of DNA methyltransferase 1, 3a, and 3b was detected in 46.8%, 32%, and 44.7% of cases, respectively. A significant correlation was found between DNA methyltransferase 1 overexpression and Scarff-Bloom-Richardson histologic grade III (P = .01). DNA methyltransferase 3a overexpression was significantly associated with menopausal status (P = .01), Scarff-Bloom-Richardson histologic grade III (P = .0001), estrogen (P = .04) and progesterone (P = .007) receptor negativity, and HER2 overexpression (P = .004). However, DNA methyltransferase 3a overexpression was found less frequently in the luminal A intrinsic breast cancer subtype (9.7%) than in luminal B (53%), HER2 (41%), and triple-negative (50%) subtypes (P = .001). DNA methyltransferase 3b overexpression shows significant correlation with promoter hypermethylation of BRCA1 (P = .03) and RASSFA1 (P = .04) and with the hypermethylator phenotype (more than 4 methylated genes, P = .01). These data suggest that overexpression of various DNA methyltransferases might represent a critical event responsible for the epigenetic inactivation of multiple tumor suppressor genes, leading to the development of aggressive forms of sporadic breast cancer.

• Authors: Riadh Ben Gacem, Mohamed Hachana, Sonia Ziadi, Soumaya Ben Abdelkarim, Samir Hidar, Mounir Trimeche
• Journal: Human pathology (Hum Pathol) Vol. 43 Issue 10 Pg. 1731-8 (Oct 2012) ISSN: 1532-8392 [Electronic] United States
• PMID: 22520950 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• DNMT3A protein, human
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases
• DNA Methyltransferase 3A
• DNA methyltransferase 3B

Topics

• Adult
• Aged
• Breast Neoplasms (enzymology, genetics, pathology)
• Carcinoma, Ductal, Breast (enzymology, genetics, pathology)
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases (analysis, biosynthesis)
• DNA Methylation
• DNA Methyltransferase 3A
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Polymerase Chain Reaction
• Promoter Regions, Genetic
• Tunisia
• Up-Regulation