Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma

Antonio Lopez-Beltran, J. L. Ordóñez, A. P. Otero, A. Blanca, V. Sevillano, M. Sanchez-Carbayo, Z. Kirkali, Liang Cheng, R. Montironi, R. Prieto, E. De Alava

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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% 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<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<0.0001). Cox's regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p=0.030, RR3.561, 95% CI 1.128-11.236) together with pT category (p<0.0001, RR5.834, 95% 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.

Original languageEnglish
Pages (from-to)559-567
Number of pages9
JournalJournal of Biological Regulators and Homeostatic Agents
Volume27
Issue number2
StatePublished - Apr 2013

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Gene Amplification
Fluorescence In Situ Hybridization
Disease-Free Survival
Urinary Bladder
Carcinoma
Urinary Bladder Neoplasms
Cyclin D3
Genes
Neoplasm Genes
Survival Analysis
Neoplasms
Immunohistochemistry
Regression Analysis
Recurrence

Keywords

  • Bladder cancer
  • CCND3
  • Cyclin D3
  • FISH
  • Gene amplification
  • Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Immunology and Allergy
  • Immunology
  • Endocrinology
  • Physiology
  • Cancer Research

Cite this

Lopez-Beltran, A., Ordóñez, J. L., Otero, A. P., Blanca, A., Sevillano, V., Sanchez-Carbayo, M., ... De Alava, E. (2013). Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma. Journal of Biological Regulators and Homeostatic Agents, 27(2), 559-567.

Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma. / Lopez-Beltran, Antonio; Ordóñez, J. L.; Otero, A. P.; Blanca, A.; Sevillano, V.; Sanchez-Carbayo, M.; Kirkali, Z.; Cheng, Liang; Montironi, R.; Prieto, R.; De Alava, E.

In: Journal of Biological Regulators and Homeostatic Agents, Vol. 27, No. 2, 04.2013, p. 559-567.

Research output: Contribution to journalArticle

Lopez-Beltran, A, Ordóñez, JL, Otero, AP, Blanca, A, Sevillano, V, Sanchez-Carbayo, M, Kirkali, Z, Cheng, L, Montironi, R, Prieto, R & De Alava, E 2013, 'Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma', Journal of Biological Regulators and Homeostatic Agents, vol. 27, no. 2, pp. 559-567.
Lopez-Beltran A, Ordóñez JL, Otero AP, Blanca A, Sevillano V, Sanchez-Carbayo M et al. Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma. Journal of Biological Regulators and Homeostatic Agents. 2013 Apr;27(2):559-567.
Lopez-Beltran, Antonio ; Ordóñez, J. L. ; Otero, A. P. ; Blanca, A. ; Sevillano, V. ; Sanchez-Carbayo, M. ; Kirkali, Z. ; Cheng, Liang ; Montironi, R. ; Prieto, R. ; De Alava, E. / Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma. In: Journal of Biological Regulators and Homeostatic Agents. 2013 ; Vol. 27, No. 2. pp. 559-567.
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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{\%} 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<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<0.0001). Cox's regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p=0.030, RR3.561, 95{\%} CI 1.128-11.236) together with pT category (p<0.0001, RR5.834, 95{\%} 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.",
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