Expression of Androgen Receptor and Cancer Stem Cell Markers (CD44+/CD24- and ALDH1+): Prognostic Implications in Invasive Breast Cancer

Nazia Riaz; Romana Idress; Sadia Habib; Iqbal Azam; El-Nasir Ma Lalani

doi:10.1016/j.tranon.2018.05.002

Expression of Androgen Receptor and Cancer Stem Cell Markers (CD44⁺/CD24^- and ALDH1⁺): Prognostic Implications in Invasive Breast Cancer

Transl Oncol. 2018 Aug;11(4):920-929. doi: 10.1016/j.tranon.2018.05.002. Epub 2018 May 31.

Authors

Nazia Riaz¹, Romana Idress², Sadia Habib³, Iqbal Azam⁴, El-Nasir Ma Lalani⁵

Affiliations

¹ Section of Breast Diseases, Department of Surgery and Center for Regenerative Medicine and Stem Cell Research, Aga Khan University, Stadium Road, 74800 Karachi, Pakistan. Electronic address: nazia.riaz@aku.edu.
² Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University, Stadium Road, 74800, Karachi, Pakistan. Electronic address: romana.idress@aku.edu.
³ Center for Regenerative Medicine and Stem Cell Research, Aga Khan University, Stadium Road, 74800, Karachi, Pakistan. Electronic address: sadia.habib@aku.edu.
⁴ Department of Community Health Sciences, Aga Khan University, Stadium Road, 74800, Karachi, Pakistan. Electronic address: iqbal.azam@aku.edu.
⁵ Center for Regenerative Medicine and Stem Cell Research; Department of Pathology and Laboratory Medicine, Aga Khan University, Stadium Road, 74800, Karachi, Pakistan. Electronic address: elnasir.lalani@aku.edu.

Abstract

Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival.

Patients and methods: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with clinicopathological variables and outcome using univariable and multivariable analysis. Survival data was computed by Kaplan Meier curves.

Results: Expression of AR was observed in 62.7% tumors whereas CD44, CD24 and ALDH1 were expressed in 61.4%, 44% and 30.1% tumors, respectively. AR expression was significantly associated with T1-T2 tumors, lower grade, estrogen and progesterone receptor expression (P < .05) and remained an independent prognostic indicator in multivariable analysis (adjusted HR 0.33, 95% CI 0.13-0.81; P = .016). Significant association was observed between concordant expression of AR and CD24 (P = .001) with a favorable impact on survival (P = .007) whereas expression of CSC phenotypes (CD44⁺, CD44⁺/CD24^- and ALDH1⁺) did not correlate with adverse outcome (P > .05). However, AR expression retained the association with better prognosis even in patients whose tumors exhibited a CSC phenotype.

Conclusions: Expression of AR and CD24 in stage I-III invasive BCa correlates with favorable clinicopathological features and delineates a subgroup of patients with better disease-free survival.