title: A systematic review and meta-analysis of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma.
abstract: 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 I(2) 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, I(2)=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I(2)=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I(2)=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I(2)=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.
authors.affiliation: Department of Urology, Princess Alexandra Hospital, Brisbane, Australia Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, University of Queensland, Brisbane, Australia Department of Surgery, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Keng Lim
authors.initials: KL
authors.lastname: Ng
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, University of Queensland, Brisbane, Australia.
authors.forename: Christudas
authors.initials: C
authors.lastname: Morais
authors.affiliation: QFAB Bioinformatics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Bernard
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Saunders
authors.affiliation: Aquesta Pathology, Brisbane, Australia.
authors.forename: Hemamali
authors.initials: H
authors.lastname: Samaratunga
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, University of Queensland, Brisbane, Australia.
authors.forename: Glenda
authors.initials: G
authors.lastname: Gobe
authors.affiliation: Department of Urology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Wood
mesh_terms: D018249:Adenoma, Oxyphilic / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: CARCINOMA; DIFFERENTIATION; IMMUNOHISTOCHEMISTRY; RENAL CANCER; TUMOUR MARKERS