title: βIII-tubulin overexpression is linked to aggressive tumor features and shortened survival in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  βIII-tubulin (TUBB3) is a microtubule component overexpression of which is found in many solid cancer types, often linked to poor patient prognosis, and has been suggested to predict failure of microtubule-targeting chemotherapeutics. This study was designed to determine prevalence and prognostic impact of TUBB3 expression in kidney cancers.
  
  
  RESULTS
  A tissue microarray (TMA) containing more than 1,200 renal tumors was analyzed by immunohistochemistry. TUBB3 expression varied markedly between the different histological subtypes and was more frequent in 105 papillary cancers (75.2 %, p < 0.0001), 38 oncocytomas (52.6 %, p < 0.0001), and 22 chromophobic carcinomas (36.4 %, p = 0.1221) than in 555 clear cell RCC (16.4 %). In clear cell cancers, strong TUBB3 positivity was linked to high Fuhrman grade (p < 0.0001), advanced stage (0.002), nodal metastases (p = 0.0433), hematogenous metastases (p = 0.0016), and shortened overall survival (p < 0.0001). Associations with outcome and tumor phenotype were inversely for papillary RCC, where TUBB3 immunostaining was linked to low tumor stage (p = 0.0012) and prolonged survival (p = 0.0043).
  
  
  CONCLUSIONS
  TUBB3 expression levels and their effects are strikingly different between ccRCC and papillary RCC. These differences may be caused by differences in VHL function between these RCC subtypes, because VHL (like TUBB3) is another strong regulator of microtubule function.
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Amir-Hossein
authors.initials: AH
authors.lastname: Rahvar
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Burdelski
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Koop
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eichelberg
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Dahlem
authors.affiliation: Martini Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. s.steurer@uke.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013557:Switzerland / Q000453:epidemiology; D014404:Tubulin / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C498585:TUBB3 protein, human; D014404:Tubulin
keywords: Microtubules; Renal cell cancer; Survival; TMA; βIII-tubulin