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

Abstract

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. © 2009 Japanese Cancer Association.