Role of polysomy 17 in transitional cell carcinoma of the bladder: immunohistochemical study of HER2eu expression and fish analysis of c-erbB-2 gene and chromosome 17.

摘要

This study investigates the potential clinical significance of c-erbB-2 gene and chromosome 17 alterations by fluorescence in situ hybridization (FISH) analysis and HER2eu overexpression by immunohistochemical staining in transitional cell carcinoma (TCC) of urinary bladder correlating the results with tumor stage and grade categories and with clinical behavior. Sixty-three cases of TCC retrieved from the files of 2 institutions were analyzed for chromosome 17 aberrations and c-erbB-2 amplification by FISH analysis and evaluated immunohistochemically for HER2eu overexpression. Five tumors were G1, 29 intermediate grade (G2), and 29 tumors high grade (G3); 32 tumors had stage Ta, 18 tumors T1, and 13 tumors T2. We found polysomy of chromosome 17 in 58.7% of TCC with average chromosome copy number >2.26; increased number of HER2eu gene copy was observed in 66.7% of tumors. C-erbB-2 amplification occurred in 6.3% of tumors. Immunohistochemically, 60.3% of TCC overexpressed HER2eu and 39.7% of tumors were negative. All tumors with polysomy showed simultaneously increase of HER2eu gene copy number of which 34/37 with protein overexpression. A statistically significant correlation between polysomy of chromosome 17 and tumor stage (P = .0003) and tumor grade (P < .0001) was found; polysomy was not seen in G1 tumors; however, 8/29 G2 tumors and 29/29 G3 tumors revealed polysomy of chromosome 17; in 8/32 Ta tumors, 14/18 T1 and 13/13 of deeply invasive tumors (T2) polysomy 17 was observed. Moreover, it was found that 7 superficial tumors (1 Ta and 6 T1) showed high polysomy with average of chromosome 17 copy number > or =3.76 as observed in all invasive tumors. The data suggest that although HER2eu amplification, found in high grade and invasive tumors, is a rare event in TCC, polysomy of chromosome 17 is an important factor correlated with tumor stage and grade categories and could be considered a molecular marker of tumor progression with interesting diagnostic implications.