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Int J Clin Exp Pathol 2013;6(6):998-1008

Original Article
Comparative expression profiling for human endoplasmic reticulum-resident
aminopeptidases 1 and 2 in normal kidney versus distinct renal cell carcinoma subtypes

Christine G Stoehr, Maike Buettner-Herold, Esther Kamphausen, Simone Bertz, Arndt Hartmann, Barbara Seliger

Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8 - 10, 91054 Erlangen, Germany; Institute of Pathology, Nephropathology,
University Hospital Erlangen, Krankenhausstr. 8 - 10, 91054 Erlangen, Germany; Institute of Medical Immunology, Martin-Luther-University
Halle-Wittenberg, Magdeburger Str. 2, D-06112 Halle (Saale), Germany

Received April 15, 2013; Accepted April 30, 2013; Epub May 15, 2013; Published June 1, 2013

Abstract: Altered expression of the ER-resident aminopeptidases ERAP1 and ERAP2 might play an important role in shaping the MHC class I-
presented peptide repertoire, but their function in tumors has not been determined in detail. Thus, the expression of ERAP1, ERAP2 and HLA
class I heavy chain (HC) was analysed in various renal tumor types and corresponding kidney parenchyma by immunohistochemistry.
Additionally, comparative expression profilings of untreated versus interferon (IFN)-γ-treated RCC cell lines were performed applying qRT-PCR,
Western blot and/or flow cytometry. Normal kidney tissues showed strong ERAP1 staining in the proximal tubules of 57.4 % of cases, in the
distal tubules of 94.3 % of cases and in the medulla of 88.6 % of cases, whereas high ERAP2 levels were observed in the medulla of 77.1 % of
cases and in both, proximal and distal tubules of about 88 % of cases. Imbalanced, downregulated and RCC subtype-specific ERAP1 or
ERAP2 expression was detected in 12.7 % or 43.8 % of samples analyzed, respectively. A coordinated downregulation of ERAPs was found in
4.8 %, an upregulation of ERAP1 or ERAP2 in 22.8 % or 2.0 % of RCC lesions. No association exists between ERAP and HLA class I HC
expression for any tissue type. A heterogeneous constitutive ERAP expression pattern was also detected in RCC cell lines with lower ERAP2
than ERAP1 expression levels, which was in 11/17 RCC cell lines inducible by IFN-γ. Conclusively, ERAP1 and ERAP2 might be involved in the
development of immune escape mechanisms of RCC. (IJCEP1304020).

Keywords: Renal cell carcinoma, ERAP, immune escape, HLA class I

Address correspondence to: Dr. Christine Stoehr, Institute of Pathology, University Hospital Erlangen, Krankenhausstraße 8 – 10, 91054
Erlangen, Germany. Phone: +49 (0) 9131 85 43609; Fax: +49 (0) 9131 85 24745; E-mail: christine.stoehr@uk-erlangen.de