Loss of the Y chromosome is a rare event in prostate cancer. Y losses occur in much higher rates in most other cancer types. For this reason, we suggest that the expression of at least one Y chromosome gene is essential for prostate epithelial cells and it is possible that such a gene could represent a suitable target for future therapy of prostate cancer.
Introduction and Objective Y chromosome losses have been associated with various malignant tumors including bladder cancer, kidney cancer and prostate cancer. Conflicting data exist on the potential prognostic role of Y chromosome losses in these urological malignancies and on whether Y losses could be age-related. The aim of this study was to further clarify the potential relevance of Y chromosome losses in these tumors with respect to tumor phenotype, clinical outcome and patient age. Methods Preexisting tissue microarrays (TMA) of bladder (573 tissue samples from male patients), kidney (447 tissue samples from male patients) and prostate cancer (3261 tissue samples) with long-term clinical follow-up data were used in this study. Y chromosome losses were analyzed by dual-labeling FISH (fluorescence in situ hybridization) using centromere Y and X probe. Results Y losses were seen in 22% of bladder cancers. There was no significant age difference between patients having tumors with (67.4 +/-2.1years) or without (67.3 +/-1.2 years) Y losses (p=0.6294). Y losses were unrelated to tumor grade (p=0.7831) and stage (p=0.6140). There was no correlation between Y losses and survival in 224 invasive urothelial cancers (pT2-4; p=0.2324). Y losses were not associated with an increased risk for recurrences in 197 analyzed pTa tumors (p=0.7649) or increased progression risk in 76 analyzed pT1 tumors (p=0.4582). In kidney cancer Y losses were seen in 23% of cases. Likewise, there was no significant age difference between patients having tumors with (59.2 +/-3.6 years) or without (61.2+/-1.5 years) Y losses (p=0.5873). Y losses were unrelated to tumor grade (p=0.3111) and tumor stage (p=0.2511). There was also no correlation between Y losses and survival (p=0.7431). Remarkably, Y losses were seen in only 13 of 2826 (0.5%) analyzable cases of prostate cancers. The number of Y chromosome losses was too low for further statistical analyses. Conclusions These data show, that Y losses are frequent in urinary bladder cancer and kidney cancer, but lack association with tumor phenotype, clinical outcome and patient age. While the mechanism for Y losses in these cancers remains unclear, our data do not suggest clinical significance. In contrast to bladder and kidney cancer, Y chromosome losses were almost absent in prostate cancer. This may suggest that prostate epithelial cells are highly dependent on proper function of at least one chromosome Y gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 322.
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