This study evaluated the expression patterns of
claudins 1, 3, 4, 7, and 8 in human
renal cell carcinomas and oncocytomas and correlated expression with patient prognosis. Tissue microarrays were created from
paraffin-embedded tissue samples from 141 patients with
renal cell carcinomas or
oncocytoma (90 clear cell, 22 papillary, 17 chromophobe
renal cell carcinomas, and 12 oncocytomas). The staining pattern for
claudins 3, 4, 7, and 8 was membranous and/or cytoplasmic, whereas
claudin 1 was predominantly membranous in both nonneoplastic renal tissue and
tumors. Negative to weak
claudin 3 staining was predominantly detected in Fuhrman's grade 1 and 2 clear cell
renal cell carcinomas (78%; P=0.016), suggesting that upregulation of
claudin 3 potentially occurs concomitantly with increasing grade of clear cell
renal cell carcinomas. In addition, Kaplan-Meier univariate analysis showed a significant inverse correlation between moderate to strong
claudin 3 and 4 expression with overall survival in clear cell
renal cell carcinomas (P=0.038 and P=0.031). Moderate to strong
claudin 7 expression was significantly more common in chromophobe
renal cell carcinomas (94%) than in oncocytomas (55%; P=0.041).
Claudin 8 staining was moderate to strong in 92% of oncocytomas, which differentiated them from papillary and clear cell
renal cell carcinomas (14 and 12%; both P<0.0001). Only negative to weak
claudin 8 staining was detected in all chromophobe
renal cell carcinomas, whereas there were no
claudin 8 negative oncocytomas and 8% exhibited a weak staining pattern (P<0.0001). Due to their distinctive expression patterns,
claudins 7 and 8 can be used as useful immunohistochemical markers for the separation of chromophobe
renal cell carcinomas from oncocytomas, whereas
claudins 3 and 4 may serve as indicators of prognosis in clear cell
renal cell carcinomas.