Abstract 3878: The different genetic alterations between Western and Chinese samples indicate alternate pathways of prostate cancer development

Abstract

Abstract Prostate cancer is the most common male cancer in Western countries, but much less frequent in Asian countries. We systematically investigated genomic changes in prostate cancers from UK and China to determine genetic similarity and difference and potential alternative mechanisms of prostate carcinogenesis in these high and low cancer incidence populations. Using Affymetrix array 6.0 microarrays, we analyzed genome-wide genomic alterations in 32 UK and 39 Chinese prostate cancer samples. Distinct difference in genomic alterations between Western and Chinese prostate cancers were found, including loss of 21q22 and PTEN deletion, which are the most common genomic changes in Western prostate cancer but rarely detected in the Chinese samples. To further evaluate the difference between Western and Chinese samples, FISH analysis for PTEN deletion and ERG rearrangements and immunohistochemistry analysis for PTEN and ERG expressions were applied to UK (n=160) and Chinese (n=143) prostate cancer tissue microarrays (TMAs). PTEN deletion and ERG rearrangements were found at a significantly higher frequency in samples from UK (42.3% and 37.4%) than China (14.3% and 7.5% respectively) (P<0.001 for both). Both PTEN (76.1% vs 36.3%, p<0.01) and ERG protein were also differentially expressed. Interestingly, the nuclear locations of ERG are also significantly different from UK and China samples. Cytoplasmic expression was significantly higher in UK (46.4%) than Chinese ones (25.0%) (p=0.001) and nuclear expression was significantly lower in UK (15.0%) than Chinese ones (34.4%) (p<0.001). The ERG cytoplasmic expression is much tighter correlated to ERG rearrangements than nuclear expression in UK cancer. We further detected that PTEN deletion and ERG rearrangements were at a higher frequency in High-grade prostatic intraepithelial neoplasia (HGPIN) lesions from UK (21.4% and 21.1% respectively) than China (both 0%). Cytoplasmic expression in UK HGPINs (50.0%) was also significantly higher than that in Chinese ones (10.0%) (p=0.002), while the nuclear expression of ERG in UK (27.8%) and Chinese (23.3%) HGPINs were similar (p=0.738). Subsequently, we found that AR CAG repeat lengths, which is associated with AR activity, is significantly shorter in the UK than Chinese patients (P<0.05). In conclusion, we compared genetic alterations in prostate cancer samples from UK and China and found there are significant differences between the two groups, commencing at pre-invasive, HGPIN, stage. Our findings suggest that tumours arise in Western and Chinese populations by alternative pathogenetic mechanisms. These alterations, differentially presented in these two populations may be key genetic changes underlying the regional/ethnic difference in clinical incidence and may be induced by specific environmental and/or genetic risk factors that Western men are exposed to. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3878. doi:10.1158/1538-7445.AM2011-3878