title: Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study.
abstract: OBJECTIVE
  Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging.
  
  
  METHODS
  This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm2. Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index.
  
  
  RESULTS
  At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period.
  
  
  CONCLUSIONS
  Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.
authors.affiliation: Department of Urology, Academisch Medisch Centrum, Postbus 22660, 1100DD, Amsterdam, Netherlands. alexandre.ingels@gmail.com.|IR4M, CNRS, Univ. Paris Sud, Université Paris-Saclay, 94805, Villejuif, France. alexandre.ingels@gmail.com.|Service d'urologie Hôpital Bicêtre, 78, rue du Général Leclerc, 94271, Le Kremlin-Bicêtre, France. alexandre.ingels@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Ingels
authors.affiliation: Department of Urology, Academisch Medisch Centrum, Postbus 22660, 1100DD, Amsterdam, Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hew
authors.affiliation: Department of Pathology, Fundació Puigvert, Universitat Autonoma de Barcelona, c/Cartagena 340-350, 08025, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Algaba
authors.affiliation: Department of Pathology, AMC University of Amsterdam, Postbus 22660, 1100DD, Amsterdam, Netherlands.
authors.forename: O J
authors.initials: OJ
authors.lastname: de Boer
authors.affiliation: Department of Urology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, Netherlands.
authors.forename: R J A
authors.initials: RJ
authors.lastname: van Moorselaar
authors.affiliation: Department of Urology, Antoni Van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Horenblas
authors.affiliation: Department of Urology, Academisch Medisch Centrum, Postbus 22660, 1100DD, Amsterdam, Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Zondervan
authors.affiliation: Department of Urology, Academisch Medisch Centrum, Postbus 22660, 1100DD, Amsterdam, Netherlands.
authors.forename: J J M C H
authors.initials: JJ
authors.lastname: de la Rosette
authors.affiliation: Department of Urology, Academisch Medisch Centrum, Postbus 22660, 1100DD, Amsterdam, Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Pilar Laguna Pes
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000378:metabolism*; D009367:Neoplasm Staging; D009392:Nephrectomy; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014746:Vimentin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX
keywords: Immunohistochemistry; Markers; Pathology; Prognostic; Renal cell carcinoma