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A systematic review and meta-analysis of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma
  1. Keng Lim Ng1,2,3,
  2. Christudas Morais2,
  3. Anne Bernard4,
  4. Nicholas Saunders5,
  5. Hemamali Samaratunga6,
  6. Glenda Gobe2,
  7. Simon Wood1
  1. 1Department of Urology, Princess Alexandra Hospital, Brisbane, Australia
  2. 2Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, University of Queensland, Brisbane, Australia
  3. 3Department of Surgery, University Malaya, Kuala Lumpur, Malaysia
  4. 4QFAB Bioinformatics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
  5. 5University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia
  6. 6Aquesta Pathology, Brisbane, Australia
  1. Correspondence to Dr Keng Lim Ng, Department of Urology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, Brisbane 4102, Queensland, Australia; kenglimng{at}


Background Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.

Methods PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I2 test of heterogeneity for multiple studies.

Results One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I2=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I2=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I2=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I2=0%).

Conclusions We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.


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