Abstract
Little is known regarding the activity and function of the androgen receptor (AR) in human breast cancer. In the present study AR was evaluated in untreated primary breast cancers using antisera to the amino- and carboxy-termini of the receptor and quantitated using colour video image analysis. A strong correlation between tissue concentration and percentage AR-positive cells was observed for each antiserum. However, comparison of percentage positive cells using the amino- and carboxy-terminal AR antisera in individual breast cancer specimens revealed a subset of tumours with discordantly increased staining for the carboxy terminus. These findings suggest the presence of amino-terminal-truncated AR in a proportion of breast cancer cells or presence of AR mutations or associated protein alterations that affect binding of the amino-terminal AR antiserum. Immunohistochemical expression of the androgen-regulated glycoprotein, apolipoprotein D (apo-D), was also evaluated in the breast cancer specimens. Focal positivity of apo-D staining, which did not always co-localise with AR-positive cells, was observed within breast tumours. Furthermore, no correlation was evident between percentage positive cells stained for AR and apo-D in breast cancer specimens. These findings indicate that, although apo-D expression is androgen regulated in human breast cancer cell lines in vitro, its expression in primary breast cancers may be regulated by other factors. The expression of AR in primary breast cancers also suggests that the receptor may be involved in tumour responsiveness or in abnormal responses to endocrine therapies.
Highlights
We recently reported that the level of androgen receptor (AR) expression in primary breast cancers was the sole predictor of response to medroxyprogesterone acetate (MPA) administered following relapse on tamoxifen therapy (Birrell et al, 1995b)
All tumours contained cells that were positively stained for AR, the proportion of immunopositive cells varied from a few to >50% of cells stained
Where Apolipoprotein D (apo-D) staining was present, immunoreactivity was focal with areas of apo-Dpositive cells among negatively stained tumour cells (Figure 1c)
Summary
At the time of surgical excision of the primary tumour, 36 breast cancer specimens were chosen at random from patients treated at the Surgical Oncology Unit, Flinders Medical Centre (Bedford Park, South Australia). Tumour size and axillary lymph node involvement were determined by the Pathology Department at Flinders Medical Centre and histological grade was determined using the Bloom and Richardson classification (Bloom and Richardson, 1957). One specimen was ductal carcinoma in situ, seven tumours (19%) were grade I, i.e. well-differentiated carcinomas, 16 tumours (44%) were grade II and 12 tumours (33%) were grade III, i.e. poorly differentiated carcinomas. ER and PR content of the tumours was routinely determined by radioligand binding (Birrell et al, 1995b) and an additional portion of each tumour specimen was embedded in Tissue-Tek OCT compound (Miles Scientific, Naperville, IL, USA) and frozen at -70°C until processed
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call