[en] 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.
Disciplines :
Oncology
Author, co-author :
Ben Gacem, Riadh
Hachana, Mohamed Ridha ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Ziadi, Sonia
Ben Abdelkarim, soumaya
Hidar, Samir
Trimeche, Mounir
Language :
English
Title :
Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers.
Publication date :
18 April 2012
Journal title :
Human Pathology
ISSN :
0046-8177
eISSN :
1532-8392
Publisher :
W.B. Saunders, Philadelphia, United States - Pennsylvania
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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