Journal
JOURNAL OF BREAST CANCER
Volume 20, Issue 1, Pages 35-44Publisher
KOREAN BREAST CANCER SOC
DOI: 10.4048/jbc.2017.20.1.35
Keywords
Breast neoplasms; Epithelial-mesenchymal transition; miR-222; Prognosis
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2015R1A2A2A01007907]
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Purpose: The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-a, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, Ncadherin, and E-cadherin) was evaluated using immunohistochemistry. Results: High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the lumina! B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. Conclusion: This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.
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