Banff, Alberta, Canada
August 9-14, 2009
Rimrock Resort Hotel
10th Banff Conference on Allograft Pathology

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Banff Initiative For Quality Assurance in Diagnostic Immunohistochemistry in Transplantation (BIFQUADIT)

Alternatives for title:
Quality Assurance in Transplantation Pathology (QUAITAP)

Proposed by:

Michael Mengel, Edmonton

Rene Rodriguez, Cleveland

Volker Nickeleit, Chapel Hill

Click here to read the article, Recommendations for Improved Standardization
of Immunohistochemistry


Over the last 10 years immunohistochemistry has become an indispensable part of anatomical pathology. The diagnosis, subtyping, and prognosis of numerous disease entities depend on immunohistochemical staining results. Furthermore, several ‘theranostics’ have been established based on immunohistochemistry. Theranostics are diagnostics test which imply a specific therapy. The most clinical relevant example for a theranostic is the assessment of the HER-2 protein in patients with breast cancer by immunohistochemistry. However, the portfolio of available antibodies suitable for application in clinical immunohistochemistry (i.e. as diagnostics, prognostics, and theranostics) is steadily growing. With this the demands for quality control, quality assurance, and highly specified medical competence in the field of immunohistochemistry is continuously increasing. Today immunohistochemistry is technically robust and widely automated. But interpretation and decision making in terms of clinical significance, reliability, and technical evolution becomes more and more challenging.

Immunohistochemistry for C4d is already part of the Banff classification for the diagnosis of antibody mediated rejection in renal allografts. Detailed criteria for the evaluation of C4d staining patterns in kidney transplants are described in the 2007 Banff up-date. At the 2009 meeting developing consensus and refinement of criteria for evaluating C4d staining in heart allografts is a major topic and pilot data will be presented on the technically and diagnostically challenging aspects of C4d staining in liver allografts.. In addition, criteria for a Banff BK nephropathy classification are under discussion and will very likely included immunohistochemistry for the detection of BK in renal tubular epithelial cells as a crucial diagnostic criterion. Obviously, based on the result of these stains significant clinical/therapeutic decisions will be made, i.e. these stains are theranostics. Thus, they fulfill the criteria of a type II clinical test and hence require appropriate quality control mechanisms. The description of specific / diagnostic staining patterns and internal control features as well as regular external quality assurance assessments are required to fulfill international standards of adequacy (see attached publication “Recommendations for Improved Standardization of Immunohistochemistry by Neal S. Goldstein, MD, Stephen M. Hewitt, MD, PhD, Clive R. Taylor, MD, DPhil, Hadi Yaziji, MD, David G. Hicks, MD, and Members of Ad-Hoc Committee On Immunohistochemistry Standardization. Appl Immunohistochem Mol Morphol 2007;15:124–133)


The BIFQUADIT proposal:

·         Establishment of a Banff subcommittee for quality assurance in diagnostic immunohistochemistry and potentially immunofluorescence

·         Elaboration of guidelines and logistics for external quality assurance trials in immunohistochemistry

·         Identification of reference centres

·         Collection of suitable test material

·         Definition of standards for strong, moderate, mild positive and negative cases

·         Collection and preparation and offering of standardized positive and negative controls

·         Organization of regular quality assurance trials for inter-laboratory and inter-observer assessment


Aim of this initiative is to guarantee highest standards for quality control, quality assurance, and medical reasonability in the area of diagnostic immunohistochemistry. BIFQUADIT will become the benchmark for diagnostic immunohistochemistry in Transplantation and can provide reference capabilities in terms of quality control for the whole community.

Using Tissue Microarrays (TMA) for quality assurance trials

·         A large number of cases, representing the whole analytical spectrum from negative to mildly, to moderately, to strongly positive, as well as cases undergone sub-optimal processing and standardized cell lines can be tested on one slide under identical staining conditions. Thus, in the participating labs no day-to-day variations in the staining protocol influence the results. The pure staining capability on a random day in the lab is tested and makes the results between all included tissues comparable, i.e. on a weak day in the lab, all staining results on the TMA are weak. A false impression of the lab would come out if the mildly positive test cases are stained on a good day and the strongly positive on a bad day and at the end both show the same result.

·         Staining only one slide per marker but obtaining numerous results per lab for the trial makes it more attractable to participate

·         Furthermore, using TMAs finite test material can be used for a high number of tests.

·         TMAs can be evaluated more rapidly

·         Overall costs are lower compared to use single tissue tests

·         The technology is available and has been applied successfully to large quality assurance trials before (see attached publications)


Example of a TMA in a quality assurance trial for estrogen receptors:

Text Box: 1.35mm = 1.4mm2






Reference List


1)            Mengel M, von Wasielewski R, Wiese B, Rudiger T, Muller-Hermelink HK, Kreipe H. Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial. J Pathol 2002; 198(3):292-299.

2)            Mengel M, Kreipe H, von Wasielewski R. Rapid and large-scale transition of new tumor biomarkers to clinical biopsy material by innovative tissue microarray systems. Appl Immunohistochem Mol Morphol 2003; 11(3):261-268.

3)            Mengel M, Hebel K, Kreipe H, von Wasielewski R. Standardized on-slide control for quality assurance in the immunohistochemical assessment of therapeutic target molecules in breast cancer. Breast J 2005; 11(1):34-40.

4)            von Wasielewski R, Mengel M, Wiese B, Rudiger T, Muller-Hermelink HK, Kreipe H. Tissue array technology for testing interlaboratory and interobserver reproducibility of immunohistochemical estrogen receptor analysis in a large multicenter trial. Am J Clin Pathol 2002; 118(5):675-682.



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