title: The diagnostic and prognostic utility of claudin expression in renal cell neoplasms.
abstract: 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.
authors.affiliation: Department of Pathology, Rhode Island Hospital, Brown Medical School, Providence, RI 02903, USA.
authors.forename: Mirna
authors.initials: M
authors.lastname: Lechpammer
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Evgeny
authors.initials: E
authors.lastname: Yakirevich
authors.forename: Wesley O
authors.initials: WO
authors.lastname: Greaves
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Sciandra
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Tavares
authors.forename: Lelia C
authors.initials: LC
authors.lastname: Noble
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DeLellis
authors.forename: Li J
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D018249:Adenoma, Oxyphilic / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D002467:Cell Nucleus / Q000473:pathology; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins; C502011:claudin 8