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

• Main Authors: Xu Jia, Tagliabue Elda, Carcangiu Maria, Zhao Naiqing, Orlandi Rosaria, Feng Weiwei, Bast Robert C, Yu Yinhua
• Format: Article
• Language: English
• Published: BMC 2010-07-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/10/378

<p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Materials and methods</p> <p>Bisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (<it>HIN-1, RASSF1A, RIL, CDH13, RARβ2 </it>and E-cadherin) in 38 pairs of primary breast tumors and lymph node metastases.</p> <p>Results</p> <p>We found that <it>HIN-1, CDH13, RIL, RASSF1A </it>and <it>RARβ2 </it>were frequently methylated both in primary and metastatic tissues (range: 55.3%~89.5%). E-cadherin was not frequently methylated in either setting (range: 18.4%~23.7%). The methylation status of <it>HIN-1, CDH13, RIL</it>, and <it>RARβ2 </it>in lymph nodes metastasis were correlated with that in primary tumors. The Pearson correlation values ranged from 0.624 to 0.472 (<it>p </it>values < 0.01 to 0.001). Interestingly, we observed an association between <it>HIN-1 </it>methylation and hormone status in metastatic lymph nodes. Hypermethylation of <it>HIN-1 </it>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).</p> <p>Conclusions</p> <p>This study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.</p>