IMAGE-ANALYSIS OF ANDROGEN RECEPTOR IMMUNOSTAINING IN PROSTATE-CANCERACCURATELY PREDICTS RESPONSE TO HORMONAL-THERAPY

Purpose: Immunostaining for androgen receptor in prostate tumor specim ens has revealed that the majority of primary and advanced stage cance rs are positive for this regulatory transcription factor. Consequently , its use as a marker for tumor behavior and therapeutic response has been discounted. However, past reports have noted significant heteroge neity of androgen receptor immunostaining between prostate tumor cells in contrast to staining homogeneity in normal epithelium, which indic ates that variability in androgen receptor content may exist within ce rtain tumor specimens. To analyze this phenomenon more thoroughly and to determine whether this variability possesses clinical correlates, a ndrogen receptor immunostaining profiles within androgen receptor posi tive prostate tumor specimens were categorized using an image analysis based system. Materials and Methods: Tumor specimens were obtained be fore hormone therapy from 44 patients with advanced stage prostate can cer and 4 with early stage disease who later had progression. Response to antiandrogen therapy and survival was monitored. Paraffin embedded tumor sections were processed for immunocytochemistry and stained for androgen receptor. A Quantimet image analysis system was used to ana lyze nuclear immunostaining for androgen receptor and Receptogram dagg er patterns were established for each specimen based on univariate dis tributions of nuclear receptor content and concentration. Results: Dat a revealed that 17 of 18 responders to hormone therapy possessed type 1 (15) or type 3 (2) Receptograms, which are characterized by a unimod al peak or multimodal peaks within a narrow concentration range. Of th e 17 cases that stabilized following therapy 16 had type 3 Receptogram s and I was characterized as type 1. In contrast, all 13 patients in w hom endocrine treatment failed had either type 2 or 4 Receptograms, wh ich are characterized by a highly skewed or bimodal androgen receptor distribution. Positive and negative predictive values for this assay w ere 100 and 93%, respectively. In addition, the type 1/3 Receptogram p atterns were correlated with longer mean survival. Conclusions: Image analysis of prostate cancer androgen receptor immunostaining with a pa ttern oriented approach for response is capable of accurately predicti ng response to hormone therapy in patients with advanced stage disease . Application of this analytic scheme may assist the clinician with th erapeutic management of advanced prostate cancer.