Prior data clearly demonstrated the expression of prostate stem cell antigen (PSCA) mRNA in prostatic intraepithelial neoplasia (PIN) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression was associated with the presence of cancer in this disease. One hundred seventeen men were diagnosed with isolated PIN on initial prostate biopsy, 51 with low-grade form (LGPIN), and 66 with high-grade form (HGPIN). PSCA mRNA expression in initial PIN and subsequent cancer was examined by in situ hybridization (ISH). The differences of the PSCA mRNA expression level between the groups were analyzed by the Chi-square and Student's t-test. Univariate and multivariate logistic regression analyses were performed to evaluate the predictive performance of PSCA mRNA. PSCA mRNA expression level in 34 subsequent cancers was statistically increased compared with their paired PIN (P < 0.001), with a Gleason's dependence. HGPIN showed statistically high PSCA mRNA expression compared with LGPIN (P < 0.01). PSCA mRNA expression levels were significantly stronger in the initial isolated LGPIN and isolated HGPIN with subsequent cancer than those without (P < 0.001 and P < 0.001, respectively). Multivariate logistic regression analysis demonstrated that only PSCA mRNA was predictive of the onset of subsequent cancer in patients with isolated LGPIN and in those with isolated HGPIN, respectively. Our data identify PSCA mRNA in initial PIN as a significant predictor of subsequent cancer, suggesting that PSCA implies in prostatic tumorigenesis and may be used to identify the patients with isolated PIN who are at high risk for cancer onset in the disease process. (c) 2007 Wiley-Liss, Inc.