title: Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.
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.
authors.affiliation: Medical Oncology d.U., Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Medical Oncology d.U., Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.affiliation: Medical Oncology d.U., Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Medical Oncology d.U., Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.affiliation: Medical Oncology d.U., Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Zambonin
authors.affiliation: Biostatistics, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Urologic Clinic, Department of Oncological and Surgical Sciences, Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Artibani
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Medical Oncology d.U., Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D046888:Tissue Array Analysis; D014404:Tubulin / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D016271:Proto-Oncogene Proteins c-myc; D014404:Tubulin