Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder

Francesco Massari, Emilio Bria, Chiara Ciccarese, Enrico Munari, Alessandra Modena, Valentina Zambonin, Isabella Sperduti, Walter Artibani, Liang Cheng, Guido Martignoni, Giampaolo Tortora, Matteo Brunelli

Research output: Contribution to journalArticle

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Abstract

Background: To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods: In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results: beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions: c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

Original languageEnglish
Article numbere0127908
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 5 2015

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Tubulin
tubulin
bladder
carcinoma
Muscle
Urinary Bladder
Carcinoma
Muscles
muscles
Biomarkers
formalin
Paraffin
alkanes
Formaldehyde
biomarkers
Cells
therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Massari, F., Bria, E., Ciccarese, C., Munari, E., Modena, A., Zambonin, V., ... Brunelli, M. (2015). Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder. PLoS One, 10(6), [e0127908]. https://doi.org/10.1371/journal.pone.0127908

Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder. / Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo.

In: PLoS One, Vol. 10, No. 6, e0127908, 05.06.2015.

Research output: Contribution to journalArticle

Massari, F, Bria, E, Ciccarese, C, Munari, E, Modena, A, Zambonin, V, Sperduti, I, Artibani, W, Cheng, L, Martignoni, G, Tortora, G & Brunelli, M 2015, 'Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder', PLoS One, vol. 10, no. 6, e0127908. https://doi.org/10.1371/journal.pone.0127908
Massari F, Bria E, Ciccarese C, Munari E, Modena A, Zambonin V et al. Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder. PLoS One. 2015 Jun 5;10(6). e0127908. https://doi.org/10.1371/journal.pone.0127908
Massari, Francesco ; Bria, Emilio ; Ciccarese, Chiara ; Munari, Enrico ; Modena, Alessandra ; Zambonin, Valentina ; Sperduti, Isabella ; Artibani, Walter ; Cheng, Liang ; Martignoni, Guido ; Tortora, Giampaolo ; Brunelli, Matteo. / Prognostic value of beta-tubulin-3 and c-Myc in muscle invasive urothelial carcinoma of the bladder. In: PLoS One. 2015 ; Vol. 10, No. 6.
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abstract = "Background: To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods: In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results: beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53{\%} low vs 12.7{\%} high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5{\%} versus 18.7{\%} versus 0{\%}, log-rank p = 0.006). Conclusions: c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.",
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AU - Bria, Emilio

AU - Ciccarese, Chiara

AU - Munari, Enrico

AU - Modena, Alessandra

AU - Zambonin, Valentina

AU - Sperduti, Isabella

AU - Artibani, Walter

AU - Cheng, Liang

AU - Martignoni, Guido

AU - Tortora, Giampaolo

AU - Brunelli, Matteo

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N2 - Background: To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods: In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results: beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions: c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

AB - Background: To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods: In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results: beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions: c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

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