Title

Lack of androgen receptor expression correlates with high expression of ALDH1 and poor overall and 5-year disease free survival in patients with invasive breast cancer

Document Type

Article

Department

Pathology and Laboratory Medicine

Abstract

Introduction: A sub-population of cells referred to as cancer stem cells has been identified utilizing specific markers such as aldehyde dehydrogenase 1 (ALDH1) amongst others in solid tumors including breast cancers. Evidence from in vitro studies has shown that high ALDH1 expression identifies tumorigenic cell population which is capable of self-renewal and generating tumors which recapitulate the heterogeneity of the primary tumors. Expression of androgen receptor is present in 70-90% cases of invasive breast cancers at a frequency that is higher than the expression of estrogen or progesterone receptors. However, prognostic relevance of androgen receptor expression in relation to the expression of ALDH1 has not been investigated.
Methodology: Immunohistochemical expression of ALDH1 and AR was evaluated in formalin fixed paraffin embedded blocks from 177 invasive breast cancer cases at a single institution in Pakistan from 2006-2010. Clinico-pathological details and follow-up data were collected from patients' medical charts. Data analysis was performed on SPSS version 19. Over-all survival and 5-year disease free survival were estimated by Kaplan Meier.
Results: The mean age of the patients was 53.9 (+ 12.40) years. Fifteen percent patients were diagnosed with stage I disease, 52% with stage II, 25% and 8% presented with stage III and stage IV disease, respectively. Twelve percent patients presented with T1 tumors, 49.7% patients presented with T2 tumors whereas 23.7% and 14.6 % patients presented with T3 and T4 tumors respectively. Fifty-seven percent patients were node positive. Estrogen and progesterone receptor expression was present in 62% and 52% of tumors respectively. HER-2/neu was overexpressed /amplified in 30% tumors. Immunohistochemical expression of androgen receptor (AR) was present in 63.8% tumors whereas ALDH1 expression was present in 28.8% tumors. Lack of androgen receptor expression was associated with high expression of ALDH1 ( p= 0.009).Cases were divided into two groups: Group1: ALDH1-/AR+ and Group 2: ALDH1+/ AR-. No significant differences were observed between these groups with respect to age, tumor size, stage of disease, HER-2 neu over-expression/amplification or nodal status. Group 1 phenotype correlated with nuclear grade I and II tumors (p <0.05), estrogen receptor (p <0.05) and progesterone receptor (p <0.05) expression. Group 2 phenotype was associated with nuclear grade III tumors (p <0.05) and estrogen and progesterone receptor negativity (p <0.05). Although not statistically significant, but a trend towards a better over-all survival and 5-year disease free survival was observed in group 1 as compared to group 2.
Conclusions:
1. Group 1 phenotype correlated with better prognostic features such as well to moderately differentiated and endocrine responsive tumors.
2. Group 2 phenotype correlated with poor prognostic features such as higher nuclear grade and lack of expression of hormone receptors.
3. Expression of stem cell marker, ALDH1, in group 2 phenotype correlated with poor over-all and 5-year disease free survival.

Publication

Molecular Cancer Research