CD44/CD24 and aldehyde dehydrogenase 1 in estrogen receptor-positive early breast cancer treated with tamoxifen: CD24 positivity is a poor prognosticator
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Yong Wha Moon1,*, Hee-Jung An2,*, Ja Seung Koo3, Gun Min Kim4, Hyunju Han5, Seho Park6, Seung Il Kim6, Hyung Seok Park6, Sewha Kim2, Seung Ki Kim7, Seung Ah Lee7, Sohyun Hwang2, Gun Woo Son1 and Joohyuk Sohn4
1Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
2Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
3Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
4Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
5Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, Korea
6Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
7Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea
*These authors have contributed equally to this work
Joohyuk Sohn, email: [email protected]
Keywords: breast cancer; estrogen-receptor positive; tamoxifen; resistance; CD24
Received: August 18, 2017 Accepted: December 05, 2017 Published: December 21, 2017
CD44+/CD24- or aldehyde dehydrogenase 1 (ALDH1) has been suggested as a potential marker for breast cancer stem cells. In the cohort of 819 patients with resected ER-positive breast cancer, the ‘5-year relapse group’ within 5 years postsurgery during adjuvant tamoxifen treatment and the ‘non-relapse group’ longer than 9 years postsurgery were defined. Paraffin-embedded tumor tissues were available in 31 patients from 5-year relapse group and 68 from the non-relapse group. CD44/ CD24 and ALDH1 expression was evaluated by immunohistochemical staining. Phenotypes of CD44/CD24 were CD44+/CD24- in one patient (1%), CD44+/CD24+in one patient (1%), CD44-/CD24+ in 12 patients (12%), and CD44-/CD24- in 67 patients (68%). Four patients (4%) showed ALDH1-positivity. Due to the rarity of CD44-positivity or ALDH1-positivity, we dichotomized the patients into CD24-positive status (13%, 13/99 patients) and CD24-negative status (87%, 86/99 patients) only based on CD24 status, and only the status of CD24 was further analyzed. CD24-positivity was higher in the 5-year relapse group (32%) than in the non-relapse group (4%). CD24-positivity was associated with negative PR (P=0.026), higher N stage (P=0.029), and higher histologic grade (P=0.034). However, in the multivariate logistic regression adjusted for the known prognostic factors, CD24-positivity was still a significant predictive factor for 5-year relapse (hazard ratio=8.5; P=0.006). Our results indicated that the expression of CD24 was a significant poor prognostic factor in ER-positive early breast cancer treated with adjuvant tamoxifen. CD24 is worth further investigation as a novel biomarker for tamoxifen resistance beyond general aggressiveness of cancer cells.
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