title: Expression patterns and prognostic role of transketolase-like 1 in muscle-invasive bladder cancer.
abstract: OBJECTIVE
  The pentose phosphate pathway (PPP) has been shown to play an important role in the metabolism of cancer cells. The transketolase-like 1 gene (TKTL1) encodes an enzyme representing an essential component of this pathway. Its expression has been demonstrated to correlate with stage and outcome in various tumors. The aim of the present study was to assess expression patterns and the prognostic role of TKTL1 in muscle-invasive bladder cancer (MIBC).
  
  
  METHODS
  The expression of TKTL1 was assessed in a tissue microarray consisting of histopathologically benign and malign tissue of 112 patients who underwent radical cystectomy due to MIBC. Cytoplasmatic and nuclear expression were assessed by immunohistochemistry and compared separately with clinicopathologic parameters and outcome.
  
  
  RESULTS
  Cytoplasmatic expression of TKTL1 was exclusively present in tumor tissue. In contrast, the proportion of nuclei positive for TKTL1 was higher in histopathologically benign tissue compared with malign tissue. No correlation was observed between cytoplasmatic or nuclear TKTL1 expression and tumor stage, grade or the presence of metastases. Patients with lymph node involvement showed a decreased frequency of cytoplasmatic expression compared with node-negative patients (p = 0.01). However, no further correlation was observed between the expression of TKTL1 and clinical outcome of patients.
  
  
  CONCLUSIONS
  The present study shows that the cytoplasmatic expression of TKTL1 is specific for MIBC tissue compared with histopathologically benign urothelium. This specific expression is present in a subgroup of MIBC potentially identifying patients with activated PPP suitable for a targeted inhibition of sugar metabolism. In contrast to other malignancies, TKTL1 shows no prognostic significance in MIBC.
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Mauro
authors.initials: M
authors.lastname: Semilia
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.affiliation: Department of Urology, University Hospital, Palermo, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pavone
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bischoff
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kühs
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Bedke
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
authors.affiliation: Department of Urology, University Hospital, Tuebingen, Germany. tilman.todenhoefer@med.uni-tuebingen.de.|Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada. tilman.todenhoefer@med.uni-tuebingen.de.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D014174:Transketolase / Q000096:biosynthesis / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C505431:TKTL1 protein, human; D014174:Transketolase
keywords: Biomarker; Bladder cancer; Diabetes; Glycolysis; Pentose phosphate; Transketolase-like 1