Tumor suppressor genes are frequently methylated in lymph node metastases of breast cancers
- Equal contributors
1 Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
2 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
3 Department of Bioinfomatics, Shanghai Medical College, Fudan University, Shanghai, China
4 Department of Experimental Therapeutics, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
BMC Cancer 2010, 10:378 doi:10.1186/1471-2407-10-378Published: 20 July 2010
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.
Materials and methods
Bisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (HIN-1, RASSF1A, RIL, CDH13, RARβ2 and E-cadherin) in 38 pairs of primary breast tumors and lymph node metastases.
We found that HIN-1, CDH13, RIL, RASSF1A and RARβ2 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 HIN-1, CDH13, RIL, and RARβ2 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.