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

Gain of sequences on chromosome arm 8q is a common feature of prostate canc er that may correlate with metastatic and androgen-independent progression. The target gene(s) for this gain is not known, although MYC is amplified i n 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 ai m in this study was to test the hypothesis that PSCA overexpression may res ult from overrepresentation of chromosome arm 8q. Twenty locally advanced p rostate cancers were analyzed by dual-probe fluorescence in situ hybridizat ion (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 M YC 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 an tibodies specific for PSCA showed a high degree of correlation between PSCA gene overrepresentation and protein overexpression. Four of 5 tumors with Al of PSCA overexpressed PSCA protein, compared with only 2/15 tumors with a normal PSCA copy number or simple gain of PSCA (P = 0.0 14). These result s demonstrate that PSCA is co-overrepresented with MYC in a majority of cas es, but may not be a necessary part of the 8q amplicon. PSCA protein overex pression can result from AI of PSCA and might be useful as a cell surface m arker on prostate cancer cells with 8q overrepresentation. Genes Chromosome s Cancer 27:95-103, 2000. (C) 2000 Wiley-Liss, Inc.