Claudin-7 and
claudin-8 code for
tight junction proteins expressed in distal nephron epithelium. In a recent
oligonucleotide microarray study, we identified claudin-7 and
claudin-8 as candidate markers to distinguish
chromophobe renal cell carcinoma from other renal
tumors, including
oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because
chromophobe renal cell carcinoma has malignant
biological potential, whereas
renal oncocytoma is benign. Claudin-7 and
claudin-8 expression was studied by immunohistochemistry in 11 chromophobe
renal cell carcinomas and 17 oncocytomas using
formalin-fixed
paraffin-embedded tissue sections of
tumor with adjacent nonneoplastic kidney.
Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon
carcinoma and adjacent nonneoplastic kidney). Claudin-7
protein was expressed in a membranous pattern in 10 of 11 chromophobe
renal cell carcinomas and 4 of 17 oncocytomas (P < .01).
Claudin-8 was expressed in multiple patterns: In
oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In
chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative
claudin-8 was seen in 7 of 11 chromophobe
renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for
chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic
claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe
renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for
oncocytoma). The distal nephron
proteins claudin-7 and
claudin-8 have potential use as immunohistochemical
biomarkers in the differential diagnosis of
chromophobe renal cell carcinoma and
oncocytoma. Expression of claudin-7 and
claudin-8 may reflect the relationship of
chromophobe renal cell carcinoma and
oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional
biomarkers to include with claudin-7 and
claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity.