The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: A retrospective study of tissue microarrays using immunohistochemistry

PLoS One. 2017 Jun 27;12(6):e0179610. doi: 10.1371/journal.pone.0179610. eCollection 2017.

Abstract

Objective: To assess the prognostic roles of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue biomarkers in localized renal cell carcinoma (RCC).

Methods: Patients who underwent a nephrectomy during 1992-2015 and had a primary specimen of their kidney tumor were included. The nine tissue biomarkers were immunohistochemically stained on tissue microarrays of RCC, and the semi-quantitative H-score, including intensity score, was used to grade the sample. The Cox proportional hazards model was used to evaluate tissue markers significant for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after adjusting for significant clinicopathological parameters.

Results: Samples from 351 RCC patients were included. The mean age of the patients was 53.9 years; the rates of pathologic T1-2/≥T3 stage, Fuhrman 1+2/3+4 grade, recurrence, and death were 269/65(80.5/19.5%), 222/107 (67.5/32.5%), 6.6%, and 10.5%, respectively. Median OS, CSS, and RFS were 220.6, 220.6, and 147.1 months, respectively. The multivariable analysis showed that pathologic T stage and Fuhrman nuclear grade were significantly associated with OS and CSS. Pathologic T stage and tumor size were associated with RFS. After adjusting for these significant prognostic clinicopathological factors, Ki-67 was significantly associated with OS (hazard ratio [HR], 2.7), CSS (HR, 3.82), and RFS (HR, 4.85) and pS6 was associated with CSS (HR, 8.63) and RFS (HR, 8.51) in the multivariable model (p<0.05).

Conclusion: pS6 and Ki-67 are significant prognostic factors of RCC; however, BAP1, PBRM1, TGase 2, PD-L1, CA9, PTEN loss, and PSMA markers did not show this association.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / metabolism
  • Antigens, Surface / metabolism
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase IX / metabolism
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality*
  • Carcinoma, Renal Cell / pathology
  • DNA-Binding Proteins
  • Disease-Free Survival
  • Female
  • GTP-Binding Proteins / metabolism
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Nuclear Proteins / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Porphyrins / metabolism
  • Prognosis
  • Protein Glutamine gamma Glutamyltransferase 2
  • Retrospective Studies
  • Sulfonamides / metabolism
  • Survival Rate
  • Tissue Array Analysis
  • Transcription Factors / metabolism
  • Transglutaminases / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin Thiolesterase / metabolism

Substances

  • Antigens, Neoplasm
  • Antigens, Surface
  • B7-H1 Antigen
  • BAP1 protein, human
  • Biomarkers, Tumor
  • CD274 protein, human
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Nuclear Proteins
  • PBRM1 protein, human
  • PS6 porphyrin
  • Porphyrins
  • Sulfonamides
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • PTEN Phosphohydrolase
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Ubiquitin Thiolesterase
  • GTP-Binding Proteins
  • CA9 protein, human
  • Carbonic Anhydrase IX

Grants and funding

This study was supported by the Korean National Cancer Center Grants (nos. 1510650-1 and 1710100-1). However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.