[246] Expression of Androgen Receptor and Its Active (Phosphorylated) Forms in Breast Cancer Progression

Qinghu Ren, Shilpa Jain, Rachel Ruoff, Liying Zhang, Victor Reuter, Jonathan Melamed, Michael Garabedian, Peng Lee, Susan Logan. New York University School of Medicine, New York, NY; Memorial Sloan Kettering Cancer Center, New York, NY

Background: Androgen receptor (AR) expression is reported in ∼70% of breast cancers. We studied the expression of AR and its phosphorylated forms at Ser-213 and Ser-650, which modulate its activity, in breast cancer and its clinicopathological correlation.
Design: Immunohistochemistry was performed using specific antibodies against AR, ARSer(P)-213 and ARSer(P)-650 in localized (n=68) and metastatic (n=32) breast cancers as well as benign controls (n=34) using tissue microarrays. Intensity levels [0 (negative) - 3 (strong)] for cytoplasmic and nuclear expression were scored, and combined with percentage of positive cells to generate a histoscore for statistical analysis with an unpaired t-test.
Results: Nuclear staining of AR is seen in all benign tissue (100%) and 64 of 96 cancers (67%). The mean expression of nuclear AR is decreased 1.9-fold in cancers compared to controls (p<0.0001) (see table). Distinct patterns of expression of ARSer(P)-213 and ARSer(P)-650 were observed in breast cancer. The nuclear staining of ARSer(P)-213 is increased in breast cancers by 1.9-fold (p=0.003), while the nuclear and cytoplasmic ARSer(P)-650 expressions are both significantly decreased in tumors (p<0.0001). Cytoplasmic ARSer(P)-650 expression is lower in high stage cancers or those with lymph node involvement (p<0.005), while cancers with distant metastasis show a higher nuclear ARSer(P)-650 expression (p<0.05). ER negative cancers show an increase in cytoplasmic ARSer(P)-213 and ARSer(P)-650 expression (p< 0.05). Compared to invasive lobular carcinoma, invasive ductal carcinoma (IDC) shows increased cytoplasmic ARSer(P)-213 and ARSer(P)-650 expression (p<0.0005).

Ratio of expression levels of AR/phosphorylated forms in clinical subgroups [statistical significance values only(p<0.05). N: nuclear; C: cytoplasmic].
 Cancer / BenignER- /ER+Ductal / LobularHigh / Low StagePositive / Negative NodeMetastasis / Localized
AR-N0.50.4----
ARSer(P)-213-N1.9-----
ARSer(P)-213-C-2.524.1---
ARSer(P)-650-N0.50.6---1.7
ARSer(P)-650-C0.61.43.00.60.6-



Conclusions: We deomonstrate up-regulation of ARSer (P)-213 expression (nuclear) and down-regulation of ARSer(P)-650 (nuclear and cytoplasmic) in breast cancer. The cytoplastmic up-regulation of both correlates with breast cancer with poor prognosis (ER negative and IDC). Up-regulation of nuclear ARSer(P)-650 expression in metastatic breast cancer suggests the phosphorylation of AR at Ser-650 may play a role in cancer progression.
Category: Breast

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 47, Monday Morning

 

Close Window