| Summary: | <p>Abstract</p> <p>Background</p> <p>Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the <it>in vivo </it>behavior of these phenomena within the same bladder tumor.</p> <p>Methods</p> <p>Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence <it>in situ </it>hybridization (FISH) with a cyclin D1 gene (<it>CCND1</it>)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed.</p> <p>Results</p> <p>Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. <it>CCND1 </it>amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes.</p> <p>Conclusions</p> <p>Complex <it>in vivo </it>behavior of <it>CCND1 </it>amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and <it>CCND1 </it>amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of <it>CCND1 </it>amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001).</p>
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