TY - JOUR
T1 - Tumor suppressor genes are frequently methylated in lymph node metastases of breast cancers
AU - Feng, Weiwei
AU - Orlandi, Rosaria
AU - Zhao, Naiqing
AU - Carcangiu, Maria L.
AU - Tagliabue, Elda
AU - Xu, Jia
AU - Bast, Robert C.
AU - Yu, Yinhua
N1 - Funding Information:
This work was supported by National Institutes of Health grants CA 80957 (for YY), Shanghai Pujiang Program 08PJ14026 (for WF), AIRC (Associazione Nazionale per la Ricerca sul Cancro) (for ET and RO). We thank Silvia Veneroni and Tissue Bank of Fondazione IRCCS Istituto Nazionale dei Tumori for sample collection and Piera Aiello for processing of tumor specimens and immunohistochemistry. We thank Dr. Jean-Pierre Issa for technical support in methylation study.
PY - 2010/7/20
Y1 - 2010/7/20
N2 - Introduction: 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.Results: 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).Conclusions: This study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.
AB - Introduction: 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.Results: 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).Conclusions: This study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.
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U2 - 10.1186/1471-2407-10-378
DO - 10.1186/1471-2407-10-378
M3 - Article
C2 - 20642860
AN - SCOPUS:77954687365
SN - 1471-2407
VL - 10
JO - BMC cancer
JF - BMC cancer
M1 - 378
ER -