title: Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma.
abstract: The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Coxs regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma.
authors.forename: A L
authors.initials: AL
authors.lastname: Beltran
authors.forename: J L
authors.initials: JL
authors.lastname: Ordonez
authors.forename: A P
authors.initials: AP
authors.lastname: Otero
authors.forename: A
authors.initials: A
authors.lastname: Blanca
authors.forename: V
authors.initials: V
authors.lastname: Sevillano
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Carbayo
authors.forename: Z
authors.initials: Z
authors.lastname: Kirkali
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: R
authors.initials: R
authors.lastname: Montironi
authors.forename: R
authors.initials: R
authors.lastname: Prieto
authors.forename: E
authors.initials: E
authors.lastname: De Alava
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D056743:Cyclin D3 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; D056743:Cyclin D3