Tumor suppressor genes are frequently methylated in lymph node metastases of breast cancers

• Published in: BMC cancer Vol. 10; no. 1; p. 378
• Main Authors: Feng, Weiwei, Orlandi, Rosaria, Zhao, Naiqing, Carcangiu, Maria Luisa, Tagliabue, Elda, Xu, Jia, Bast, Jr, Robert C, Yu, Yinhua
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.07.2010; BioMed Central; BMC
• Subjects: Adult; Aged; Breast - metabolism; Breast - pathology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cadherins - genetics; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - secondary; Carcinoma, Lobular - genetics; Carcinoma, Lobular - secondary; Case-Control Studies; Cytokines - genetics; Development and progression; DNA damage; DNA Methylation; DNA-Binding Proteins - genetics; Female; Genes, Tumor Suppressor; Genetic aspects; Humans; Immunoenzyme Techniques; LIM Domain Proteins; Lymphatic metastasis; Middle Aged; Neoplasm Staging; Physiological aspects; Polymerase Chain Reaction; Prognosis; Promoter Regions, Genetic - genetics; Receptors, Estrogen - metabolism; Receptors, Retinoic Acid - genetics; Risk factors; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; United States; China
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-378

Metastasis represents a major adverse step in the progression of breast carcinoma. Lymph node invasion is the most relevant prognostic factor; however little is known on the molecular events associated with lymph node metastasis process. This study is to investigate the status and role of methylation in lymph node metastatic tumors. Bisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (HIN-1, RASSF1A, RIL, CDH13, RARbeta2 and E-cadherin) in 38 pairs of primary breast tumors and lymph node metastases. We found that HIN-1, CDH13, RIL, RASSF1A and RARbeta2 were frequently methylated both in primary and metastatic tissues (range: 55.3% approximately 89.5%). E-cadherin was not frequently methylated in either setting (range: 18.4% approximately 23.7%). The methylation status of HIN-1, CDH13, RIL, and RARbeta2 in lymph nodes metastasis were correlated with that in primary tumors. The Pearson correlation values ranged from 0.624 to 0.472 (p values < 0.01 to 0.001). Interestingly, we observed an association between HIN-1 methylation and hormone status in metastatic lymph nodes. Hypermethylation of HIN-1 in metastasis lymph nodes was significantly associated with expression of ER (odds ratio, 1.070; P = 0.024) and with PR (odds ratio, 1.046; P = 0.026). This study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.