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Immunohistochemical Localization of RPA-1; Comment on Paper by Zhang et al., Toxicol Pathol 36;397

AstraZeneca Safety Assessment, Macclesfield, United Kingdom

The field of biomarkers of efficacy and toxicity is undergoing rapid growth, and a wide range of novel antigens is being evaluated once antibody reagents become available. In addition to analytical and biological evaluation in appropriate biofluids (plasma, urine, CSF, etc.), it is important to anchor the bio-marker to a specific pathology and site of tissue expression. Immunohistochemistry provides persuasive evidence for cell and tissue specificity as site of origin of a novel biomarker prior to entry into biofluids. The recent paper by Zhang et al. (Toxicol Pathol36;397) dramatically demonstrates cell type specificity with the example of RPA-1, a rat collecting duct marker (see front cover of volume 36, issue number 3). The authors claim additional induction of RPA-1 expression in cortical proximal tubules by IHC following gentamycin treatment (see Figure 3). However, closer inspection of the images showing the "enhanced S1/S2 segment expression" reveals that the stained cells are clearly necrotic. The IHC methods employed omission of the primary antibody as the negative control because the correct isotype control was not available from the antibody vendor, despite other mouse control IgGs being available from other vendors. In my experience, any novel IHC method must include relevant controls being conducted prior to publication so that misleading observations, for example, false-positive staining of necrotic cells, do not confound studies on novel biomarkers. RPA-1 is an excellent collecting duct injury marker in the rat, but I am not persuaded that it can be induced in the proximal tubule of the kidney based on the published evidence.

This version was published on October 1, 2008

Toxicologic Pathology, Vol. 36, No. 6, 890 (2008)
DOI: 10.1177/0192623308323625


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This Article Free Full Text (Free PDF) Free All Versions of this Article: 0192623308323625v1 36/6/890    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Betton, G. Search for Related Content PubMed PubMed Citation Articles by Betton, G. Social Bookmarking                         What's this?