title: Claudin-7 immunohistochemistry in renal tumors: a candidate marker for chromophobe renal cell carcinoma identified by gene expression profiling.
abstract: BACKGROUND
  The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas oncocytoma is benign. Furthermore, chromophobe RCC has distinct malignant potential and prognosis compared with eosinophilic variants of other RCC subtypes. Immunohistochemistry is useful for distinguishing chromophobe RCC from other subtypes of renal carcinoma, but no expression marker reliably separates chromophobe RCC from oncocytoma.
  
  
  OBJECTIVE
  In a previous gene expression microarray analysis of renal tumor subtypes, we found the distal nephron markers claudin-7 and claudin-8 to be overexpressed in chromophobe RCC versus oncocytoma and other tumor subtypes. We have confirmed similar findings in independent microarray data and validated differential claudin-7 protein expression by immunohistochemistry.
  
  
  METHODS
  Immunohistochemical analysis of claudin-7 in 36 chromophobe RCCs, 43 oncocytomas, 42 clear cell RCCs, and 29 papillary RCCs.
  
  
  RESULTS
  Membranous claudin-7 expression was detected in 67% chromophobe RCCs, compared with 0% clear cell RCCs, 28% papillary RCCs, and 26% oncocytomas (P < .001).
  
  
  CONCLUSIONS
  Based on microarray and immunohistochemical data, we propose claudin-7 to be a candidate expression marker for distinguishing chromophobe RCC from other renal tumor subtypes, including the morphologically similar oncocytoma. The clinical utility of claudin-7 should be validated in independent studies of renal tumors, possibly in combination with additional targets in a multiplex immunohistochemical panel.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hornsby
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Maria M
authors.initials: MM
authors.lastname: Picken
authors.forename: Diane
authors.initials: D
authors.lastname: Lawson
authors.forename: Qiqin
authors.initials: Q
authors.lastname: Yin-Goen
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Young
mesh_terms: D018249:Adenoma, Oxyphilic / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D057167:Claudins; D003937:Diagnosis, Differential; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C473255:CLDN7 protein, human; D057167:Claudins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm