title: p63, CK7, PAX8 and INI-1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high-grade tumours of the renal collecting system.
abstract: OBJECTIVE
  High-grade, poorly differentiated, infiltrative carcinomas involving the renal sinus region often pose challenging differential diagnostic considerations, specifically differentiation of urothelial carcinoma (UC) from renal cell carcinoma (RCC) subtypes. Accurate classification, especially the distinction of UC from RCC, is critical, as therapeutic approaches differ.
  
  
  RESULTS
  Cluster analysis was performed on immunohistochemical data from 18 invasive UCs, six CDCs, two RMCs, 18 type 2 papillary renal cell carcinomas (PRCCs) and 20 high-grade clear cell renal cell carcinomas (CRCCs) using a broad panel of traditional and novel immunohistochemical markers. The initial analysis with all antibodies segregates almost all the RCCs (45 of 46, 98%) from all the UCs based on the lack of expression of p63 in all (100%) RCCs, along with predominant strong expression of paired box gene 8 (PAX8) and vimentin, predominant lack of expression of high molecular weight cytokeratin (HMCK) and CK7 and variable expression of RCC, CD10, CA1X and PAX2. All the UCs cluster together with strong, diffuse reactivity for p63, predominant reactivity for CK7 and high molecular weight kininogen (HMWK), and absent to minimal staining with PAX8, RCC antigen, PAX2, alpha-methylacyl-CoA racemase (AMACR), carbonic anhydrase IX (CAIX) and vimentin. After removing antibodies with significant overlap and/or minimal impact, a second analysis with a limited panel including p63, CK7, vimentin, integrase interactor 1 (INI-1) and PAX8 was performed. Again, the majority of UCs cluster into one group and p63 positivity separates all UCs from RCCs.
  
  
  CONCLUSIONS
  Lack of INI-1 expression, noted exclusively in RMCs, segregates RMCs into a separate cluster. PAX8 is rarely positive (17%) in UC, is commonly expressed in CDC, RMC, PRCC and CRCC and is superior to PAX2.
authors.affiliation: Department of Pathology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0602, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Carvalho
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D006801:Humans; D053552:Keratin-7 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D000071796:SMARCB1 Protein; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D053552:Keratin-7; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins