title: 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 Western 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.
authors.affiliation: The State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
authors.forename: Jun-Hang
authors.initials: JH
authors.lastname: Luo
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Hua
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Rao
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012008:Recurrence; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D010448:Peptide Initiation Factors; D012333:RNA, Messenger; C425967:eIF-5A2