Protein expression and amplification of AIB1 in human urothelial carcinoma of the bladder and overexpression of AIB1 is a new independent prognostic marker of patient survival.
AIB1, a candidate oncogene in human breast cancer, is frequently amplified and overexpressed in several types of human cancers, but the status of AIB1 amplification and expression in urothelial carcinoma of the bladder (UC) and its clinical/prognostic significance is unclear. In our study, the methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of AIB1 in 163 primary UCs and in 30 samples of normal bladder mucosa. Overexpression of AIB1 and amplification of AIB1 was found in 32.5 and 7.0% of UCs, respectively. In univariate survival analysis of the UC cohorts, a highly significant association of overexpression of AIB1 with shortened patient survival (mean: 45.6 months vs. 59.0 months, p < 0.001, log rank test) was demonstrated. In different subsets of UC patients, overexpression of AIB1 was also a prognostic indicator in grade 1 (p = 0.007), grade 2 (p = 0.010) and grade 3 (p = 0.015) tumor patients, and in pTa (p = 0.025), pT2-4 (p = 0.004), pN0 (p < 0.001) and pT2-4/pN0 (p = 0.040) tumor patients. Importantly, AIB1 expression (p < 0.001) together with pT and pN status (p < 0.05) provided significant independent prognostic parameters in multivariate analysis. In addition, a significant correlation (p < 0.05) of overexpression of AIB1 with an increased UC labeling index of Ki-67 (a cell proliferation marker) was observed in these UCs. Thus, these findings provide evidence that an overexpression of AIB1, as detected by immunohistochemistry, is an independent molecular marker for poor prognosis (shortened survival time) of patients with UC.
Luo
Jun-Hang
JH
The State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Xie
Dan
D
Liu
Meng-Zhong
MZ
Chen
Wei
W
Liu
Yong-Dong
YD
Wu
Guo-Qing
GQ
Kung
Hsiang-Fu
HF
Zeng
Yi-Xin
YX
Guan
Xin-Yuan
XY
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D056921:Nuclear Receptor Coactivator 3; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D015534:Trans-Activators / Q000032:analysis*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology; D019459:Urothelium / Q000737:chemistry* / Q000473:pathology
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3