Coamplification of prostate stem cell antigen (PSCA) and MYC in locally advanced prostate cancer

Abstract

Gain of sequences on chromosome arm 8q is a common feature of prostate cancer that may correlate with metastatic and androgen-independent progression. The target gene(s) for this gain is not known, although MYC is amplified in a subset of advanced tumors and is one potential candidate. Prostate stem cell antigen (PSCA) is a prostate-specific cell surface protein that maps to chromosome region 8q24.2 and is overexpressed in prostate cancer. Our aim in this study was to test the hypothesis that PSCA overexpression may result from overrepresentation of chromosome arm 8q. Twenty locally advanced prostate cancers were analyzed by dual-probe fluorescence in situ hybridization (FISH) for alterations of MYC and PSCA. Extra copies of MYC were found in 12/20 (60%) tumors, including 5 (25%) with simple gain (no increase in MYC copy number relative to the chromosome 8 centromere) and 7 (35%) with an additional increase (AI or overrepresentation) in MYC copy number relative to the centromere. In the five cases with simple gain of MYC, there was a concomitant gain of PSCA. PSCA was overrepresented in 5/7 (71%) cases with AI of MYC. Immunohistochemical staining of the 20 tumors with monoclonal antibodies specific for PSCA showed a high degree of correlation between PSCA gene overrepresentation and protein overexpression. Four of 5 tumors with AI of PSCA overexpressed PSCA protein, compared with only 2/15 tumors with a normal PSCA copy number or simple gain of PSCA (P = 0.014). These results demonstrate that PSCA is co-overrepresented with MYC in a majority of cases, but may not be a necessary part of the 8q amplicon. PSCA protein overexpression can result from AI of PSCA and might be useful as a cell surface marker on prostate cancer cells with 8q overrepresentation.