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

World J Urol. 2017 Jan;35(1):81-87. doi: 10.1007/s00345-016-1854-y. Epub 2016 May 20.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC.

Keywords: Immunohistochemistry; Markers; Pathology; Prognostic; Renal cell carcinoma.

Publication types

  • Validation Study

MeSH terms

  • Aged
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase IX / metabolism*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Cause of Death
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Male
  • Middle Aged
  • Mortality
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Staging
  • Nephrectomy
  • PTEN Phosphohydrolase / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism
  • Vimentin / metabolism*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Vimentin
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX