title: Cyclin D3 gene amplification in bladder carcinoma in situ.
abstract: Carcinoma in situ (CIS) is a non-papillary high-grade, potentially aggressive, and unpredictable manifestation of bladder urothelial carcinoma. The aim of this study was to assess patterns of Cyclin D3 gene amplification in Bacillus Calmette-Guerin (BCG)-treated CIS and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 28 primary (isolated) or secondary (concomitant) bladder CIS samples in which there was enough tissue material to assess Cyclin D3 gene status by fluorescent in situ hybridization was the study group. Cyclin D3 gene amplification was present in 29% of secondary CIS; none of primary CIS samples had Cyclin D3 gene amplification. Cyclin D3 amplification was related to recurrence- (p = 0.046) and progression-free survival (p = 0.002). Type of bladder CIS (primary vs. secondary) was unrelated to recurrence- or progression-free survival in the current series. Cox's regression analysis selected Cyclin D3 as an independent predictor of progression-free survival (p = 0.041, relative risk = 61.503, 95% confidence interval = 1.1-274.710). None of primary CIS cases recurred on follow-up; nine secondary CIS recurred and four of them progressed to invasive bladder carcinoma HG T1 (n = 1), T2b N0M0 (n = 1), T3b N1M0 (n = 1) and T4aN1M1 (n = 1). Mean recurrence ± SD (months) occurred at 19.5 ± 2.06 (95% (confidence interval (CI)), 15.5-23.6); mean progression (months) occurred at 23.8 ± 1.46 (95% (CI), 20.9-26.7). Our study suggests that Cyclin D3 gene amplification might be a predictor of aggressiveness in BCG-treated CIS.
authors.affiliation: Department of Pathology, Cordoba University Medical School, Spain. em1lobea@uco.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ordóñez
authors.forename: Ana P
authors.initials: AP
authors.lastname: Otero
authors.forename: Ana
authors.initials: A
authors.lastname: Blanca
authors.forename: Vicky
authors.initials: V
authors.lastname: Sevillano
authors.forename: Marta
authors.initials: M
authors.lastname: Sanchez-Carbayo
authors.forename: Elisa
authors.initials: E
authors.lastname: Muñoz
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Enrique
authors.initials: E
authors.lastname: de Alava
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D056743:Cyclin D3 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality
chemical_list: D001500:BCG Vaccine; D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; D056743:Cyclin D3
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