Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

Abstract

This study investigates the potential clinical significance of c-erbB-2 gene and chromosome 17 alterations by fluorescence in situ hybridization (FISH) analysis and HER2/neu 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 HER2/neu 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 HER2/neu 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 HER2/neu and 39.7% of tumors were negative. All tumors with polysomy showed simultaneously increase of HER2/neu 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 ≥3.76 as observed in all invasive tumors. The data suggest that although HER2/neu 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.