Claudin-7 and claudin-8

immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma

Adeboye O. Osunkoya, Cynthia Cohen, Diane Lawson, Maria M. Picken, Mahul Amin, Andrew N. Young

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)206-210
Number of pages5
JournalHuman Pathology
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

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Renal Cell Carcinoma
Oxyphilic Adenoma
Differential Diagnosis
Claudins
Nephrons
Kidney
Sensitivity and Specificity
Biomarkers
Immunohistochemistry
Renal oncocytoma
claudin 8
Tight Junction Proteins
Steam
Oligonucleotide Array Sequence Analysis
Paraffin
Formaldehyde
Microscopy
Neoplasms
Colon
Epithelium

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Claudin-7 and claudin-8 : immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma. / Osunkoya, Adeboye O.; Cohen, Cynthia; Lawson, Diane; Picken, Maria M.; Amin, Mahul; Young, Andrew N.

In: Human Pathology, Vol. 40, No. 2, 01.02.2009, p. 206-210.

Research output: Contribution to journalArticle

Osunkoya, Adeboye O. ; Cohen, Cynthia ; Lawson, Diane ; Picken, Maria M. ; Amin, Mahul ; Young, Andrew N. / Claudin-7 and claudin-8 : immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma. In: Human Pathology. 2009 ; Vol. 40, No. 2. pp. 206-210.
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