Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): Inter-Observer and Inter-Laboratory Reproducibility for C4d Immunohistochemistry in Renal Allografts
Samantha Chan, Jessie Climenhaga, Parmjeet Randhawa, Heinz Regele, Yael Kushner, Robert Colvin, Michael Mengel. University of Alberta, Edmonton, Canada; University of Pittsburgh, Pittsburgh; University of Vienna, Vienna, Austria; MGH, Harvard Medical School, Boston
Background: Detection of C4d is crucial for diagnosing antibody mediated rejection in kidney, pancreas, and heart allografts, yet formal reproducibility studies are limited.
Design: We conducted an international multi-center trial to assess the inter-observer and inter-laboratory reproducibility for C4d immunohistochemistry on paraffin-sections. A tissue microarray (TMA) was constructed comprising 44 kidney allograft specimens representing the whole analytical spectrum from negative over mild/focal to strong/diffuse C4d positivity, in cases with acute or chronic antibody mediated rejection. Using TMAs allowed us to distribute essentially identical trial material to 78 participants at 60 institutions. Participating laboratories stained the TMA slides using local protocols. Participants evaluated their slides following the Banff C4d grading schema and entered their scores online. Stained slides were returned for centralized panel scoring. Weighted kappa statistics were used to determine the inter-observer and inter-laboratory reproducibility.
Results: Inter-observer reproducibility for comparing local participant scoring to the corresponding panel scores was fair (kappa 0.39), while inter-laboratory reproducibility based on the panel scores was moderate (kappa 0.49). Inter-observer reproducibility was primarily limited due to cases with focal staining (i.e. C4d 1-2), and could be significantly improved by omitting the Banff C4d grading schema and only considering +/- calls (kappa 0.60). Scoring only C4d+/- the inter-laboratory reproducibility improved considerably (kappa 0.78).
Conclusions: These results indicated that C4d staining on paraffin section is reproducible between laboratories. The Banff grading schema has lower reproducibility between observers, mainly due to cases with mild/focal staining patterns.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 265, Wednesday Afternoon