Claudin-7 immunohistochemistry in renal tumors: a candidate marker for chromophobe renal cell carcinoma identified by gene expression profiling.
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.
Hornsby
Christopher D
CD
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA.
Cohen
Cynthia
C
Amin
Mahul B
MB
Picken
Maria M
MM
Lawson
Diane
D
Yin-Goen
Qiqin
Q
Young
Andrew N
AN
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
D014408:Biomarkers, Tumor; C473255:CLDN7 protein, human; D057167:Claudins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm