Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as an indicator for poor clinical outcome and tamoxifen resistance
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Jae Moon Gwak1,2, Milim Kim3, Hyun Jeong Kim3, Min Hye Jang4, So Yeon Park1,3
1Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
2Green Cross Laboratory, Yongin, Republic of Korea
3Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
4Department of Pathology, Yeungnam University Medical Center, Daegu, Republic of Korea
So Yeon Park, email: [email protected]
Keywords: Oct4, breast cancer, cancer stem cell, prognosis, tamoxifen resistance
Received: September 20, 2016 Accepted: March 21, 2017 Published: March 31, 2017
The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog, Bmi1, and Klf4, are known to be associated with stemness, epithelial–mesenchymal transition and aggressive tumor behavior. This study was designed to evaluate the clinicopathological significance of their expression in breast cancer. Immunohistochemistry for Oct4, Sox2, Nanog, Bmi1, and Klf4 was performed in 319 cases of invasive breast cancer. The relationship between the expression of these markers and clinicopathologic features of the tumors, including breast cancer stem cell phenotype and epithelial–mesenchymal transition marker expression, and their prognostic value in breast cancer, were analyzed. Expression of Oct4 and Sox2 was commonly associated with high histologic grade and high Ki-67 index in the whole group and in the hormone receptor-positive subgroup. On the other hand, expression of Nanog, Bmi1, and Klf4 was inversely correlated with aggressive features of the breast cancer. Oct4 expression was associated with ALDH1 expression but not with epithelial–mesenchymal transition marker expression. In survival analysis, Oct4 expression was independently associated with poor prognosis in the whole group and in the hormone receptor-positive subgroup, but not in hormone receptor-negative subgroup. Particularly, Oct4 expression was associated with poor clinical outcome in patients with hormone receptor-positive breast cancer treated with tamoxifen. Our results indicate that Oct4 expression is associated with aggressive features, ALDH1 expression, tamoxifen resistance and poor clinical outcomes in hormone receptor-positive breast cancer, and thus may be useful as a predictive and prognostic marker in this subgroup of breast cancer.
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