CD44/CD24 and aldehyde dehydrogenase 1 in estrogen receptor-positive early breast cancer treated with tamoxifen: CD24 positivity is a poor prognosticator.

Yong Wha Moon,Ja Seung Koo,Gun Woo Son,Gun Min Kim,Hyunju Han,Seung Il Kim,Sohyun Hwang,Hee-Jung An,Seho Park,Hyung Seok Park,Sewha Kim,Seung Ah Lee,Joohyuk Sohn,Seung Ki Kim

doi:10.18632/oncotarget.23519

Yong Wha Moon, Ja Seung Koo + Show 12 more

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https://doi.org/10.18632/oncotarget.23519

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Journal: Oncotarget	Publication Date: Dec 21, 2017
Citations: 14	License type: cc-by

Affiliation: CHA Bundang Medical Center, Yonsei University

Abstract

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.

Highlights

Breast cancer is the most common cancer in women worldwide
Due to the rarity of CD44-positivity or aldehyde dehydrogenase 1 (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
Our results indicated that the expression of CD24 was a significant poor prognostic factor in estrogen receptor (ER)-positive early breast cancer treated with adjuvant tamoxifen

Summary

Introduction

Breast cancer is the most common cancer in women worldwide. Despite advances in detection and development of new treatment approaches, this disease has a high mortality rate due to the emergence of therapyresistant cancer cells. [1] This resistance phenomenon applies to tamoxifen therapy. In estrogen receptor (ER)-positive breast cancer, adjuvant tamoxifen reduces the risk of recurrence by approximately 50%, [2] many patients who receive tamoxifen as an adjuvant therapy eventually experience disease recurrence. This primary or acquired resistance to tamoxifen is a serious clinical problem. The other explanation is that cells with tumorigenic potential are intrinsically resistant to therapy In this case, the relative proportion of cells in residual tumors with tumorigenic properties would be expected to increase after treatment. The relative proportion of cells in residual tumors with tumorigenic properties would be expected to increase after treatment This concept parallels with the cancer stem cell theory

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