Overexpression of EIF‐5A2 predicts tumor recurrence and progression in pTa/pT1 urothelial carcinoma of the bladder

The authors investigated the status of abnormalities of eIF‐5A2 gene in superficial (pTa/pT1) urothelial carcinoma of the bladder (UC), as well as its correlation with clinicopathologic variables and patient outcome. The methods of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), reverse transcription‐polymerase chain reaction (RT‐PCR) and Wetern blotting were utilized to examine protein/mRNA(messenger RNA) expression and amplification of eIF‐5A2 in a cohort of pTa/pT1 UCs. Overexpression of EIF‐5A2 was examined by IHC in 38/112 (33.9%) pTa/pT1 UCs. A significant association of overexpression of EIF‐5A2 with shortened UC patient recurrence‐free survival ( P =  0.002), as well as with shortened progression‐free survival ( P =  0.004), was demonstrated. Importantly, multivariate Cox regression analysis revealed that EIF‐5A2 expression provided a significant independent prognostic parameter either in tumor recurrence ( P =  0.002) or in tumor progression ( P =  0.007). FISH results demonstrated that eIF‐5A2 amplification was detected in 5/59 of the informative UCs; in each of the five cases with eIF‐5A2 amplification, overexpression of EIF‐5A2 was observed. In the remaining 54 UCs without eIF‐5A2 amplification, 16 cases were also observed to have overexpression of EIF‐5A2. In 13 pairs of UC and adjacent normal tissues, eight UCs were examined and showed up‐regulated eIF‐5A2 mRNA by RT‐PCR, while increased expression of EIF‐5A2 protein was only detected in 4/8 UCs by Western blotting. These findings suggest that overexpression of EIF‐5A2, as detected by IHC, may predict tumor recurrence and progression in pTa/pT1 UC patients, and the protein expression of eIF‐5A2 might be regulated not only by gene amplification, but also by other molecular mechanisms. ( Cancer Sci 2009; 100: 896–902)