In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1730-1730
Abstract:
Background: Estrogen receptor (ER) is an important prognostic biomarker in breast cancer. Epigenetic silencing of ESR1 could be of important clinical significance especially for its potential impact on endocrine treatment efficacy. Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of CTCs and ctDNA. Our group has evaluated for the first time epigenetic silencing of tumor and metastasis suppressor genes in CTCs and corresponding ctDNA. In this study, we evaluated for the first time ESR1 methylation in CTCs, paired ctDNA and primary tumors of breast cancer patients. Methods: We developed and validated a highly sensitive and specific real-time MSP assay for ESR1 methylation. We further applied the developed assay in sodium bisulfite (SB) treated DNA samples from: a) FFPEs from 40 patients with operable breast cancer, 25 patients with metastasis, 30 mammoplasties and 15 fibroadenomas, b) EpCAM+ immunomagnetically isolated CTCs fractions, from 74 early breast cancer patients, 48 patients with metastasis and 30 healthy donors, c) CellSearch® cartridges from 36 early breast cancer patients, 22 patients with metastasis, d) ctDNA isolated from plasma of matched samples and 54 healthy donors as a control group. Results: By using this highly specific and sensitive assay (sensitivity 0.1%) we detected methylation of ESR1 in: a) FFPEs: 16/40(40%) early breast cancer patients, 9/25(36%) patients with verified metastasis, 7/30(23.3%) mammoplasties and 5/15(33.3%) fibroadenomas. A statistically significant negative correlation was observed between ESR1 methylation status and ER protein expression (56/65 samples, 86%, p & lt;0.001). b) In EpCAM+ CTCs fraction samples: ESR1 was found methylated in 16/74(21.6%) operable breast cancer patients, 10/48(20.8%) patients with metastasis, but only in 1/30(3.3%) healthy donors. c) CTC+ CellSearch® cartridges: 3/13(23.1%) in early breast cancer and 2/7(28.6%) in patients with metastasis. d) In ctDNA: ESR1 methylation was observed in 3/36(8.3%) early breast cancer patients, 3/22(13.6%) patients with metastasis and 2/54(3.7%) samples in the control group. ESR1 methylation status was highly correlated when paired DNA from CellSearch® cartridges and corresponding ctDNA samples were compared; 36/36 (100%, p & lt;0.001) in early breast cancer and 21/22 (95.5%, p & lt;0.001) in metastasis. Conclusions: ER expression and ESR1 methylation were found 100% inversely correlated in primary tissues. The EpCAM+ CTC fraction of patients with breast cancer was found methylated for ESR1. Interestingly, ESR1 methylation was detected exclusively in CTC+ samples as analyzed from CellSearch® cartridges but in none of CTC- samples. In paired plasma samples, ESR1 methylation showed a high concordance (p & lt;0.001) with ESR1 methylation in CTCs. Additional studies are needed to further evaluate the clinical significance of our findings. Citation Format: Sophia Mastoraki, Areti Strati, Eleni Tzanikou, Eleni Politaki, George Koutsodontis, Loukas Kaklamanis, Nikolaos Malamos, Amanda Psyrri, Vassilis Georgoulias, Evi Lianidou. ESR1 methylation in circulating tumor cells, ctDNA and primary tumors of breast cancer patients [abstract] . In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1730. doi:10.1158/1538-7445.AM2017-1730
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-1730
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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