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Global DNA hypomethylation in breast carcinoma
Author(s) -
Soares Jorge,
Pinto António E.,
Cunha Celso V.,
André Saudade,
Barão Isabel,
Sousa J. Meneses,
Cravo Marília
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990101)85:1<112::aid-cncr16>3.0.co;2-t
Subject(s) - dna methylation , pathology , breast carcinoma , carcinoma , medicine , progesterone receptor , breast cancer , biology , estrogen receptor , cancer research , cancer , gene expression , biochemistry , gene
BACKGROUND The global DNA methylation of 136 breast lesions (117 primary invasive carcinomas, 5 benign phyllodes tumors, 11 fibroadenomas, and 3 sclerosing adenosis) and their respective adjacent parenchyma was analyzed using an in vitro enzyme assay. METHODS In the group of patients with breast carcinoma, DNA hypomethylation was correlated with clinical and pathologic parameters known to affect disease prognosis. Histopathologic type, disease stage, and tumor grade were evaluated according to the World Health Organization classification, the TNM system, and the criteria of Elston and Ellis' criteria, respectively. DNA flow cytometry was performed in fresh/frozen samples stained with propidium iodide. Hormone receptor (estrogen and progesterone receptor) status was determined by immunocytochemistry. RESULTS The comparative study of DNA methylation showed that the DNA of breast carcinomas was statistically significantly less methylated than the DNA of the respective adjacent parenchyma ( P = 0.0001), the DNA of breast benign lesions ( P = 0.0002), and the DNA of normal parenchyma ( P < 0.0001). A statistically significant correlation was found between the global DNA hypomethylation and the disease stage ( P = 0.0009), tumor size ( P = 0.0026), and histologic grade ( P = 0.0097) of malignant neoplasms. A trend for DNA from breast carcinomas with positive axillary lymph nodes (N1) to be more hypomethylated than those without nodal involvement (N0) ( P = 0.055) was verified. In contrast, no significant association was found between DNA methylation and histologic type of tumors, hormone receptors, DNA ploidy, and S‐phase fraction. CONCLUSIONS The current shows that DNA hypomethylation is increased in breast carcinomas, playing a potentially important role in tumor development. These findings also suggest that DNA methylation status may be a biologic marker with prognostic significance in this group of neoplasms. Cancer 1999;85:112–8. © 1999 American Cancer Society.