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. 2015 Jun 5;10(6):e0127908.
doi: 10.1371/journal.pone.0127908. eCollection 2015.

Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

Francesco Massari  1 , Emilio Bria  1 , Chiara Ciccarese  1 , Enrico Munari  2 , Alessandra Modena  1 , Valentina Zambonin  1 , Isabella Sperduti  3 , Walter Artibani  4 , Liang Cheng  5 , Guido Martignoni  2 , Giampaolo Tortora  1 , Matteo Brunelli  2
Affiliations

Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

Francesco Massari et al. PLoS One. .

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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. A] c-Myc iperexpression (2+); B] absence of expression of c-Myc.
Fig 2
Fig 2. A] strong positive beta-3-tubulin expression versus absence cores B) 2+ beta-3-tubulin expression.
Fig 3
Fig 3. Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to c-Myc.
Fig 4
Fig 4. Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to beta-3-tubulin.
Fig 5
Fig 5. Unudjested Kaplan-Meier curves for Event-free Survival (A) and Overall Survival (B) according to the combination of c-Myc and beta-3-tubulin.
See this image and copyright information in PMC

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