External quality assessment for PD-L1
Immunohistochemistry (IHC) for PD-L1 protein is a new central predictive test for different cancers. In treatment of non-small-cell lung cancer (NSCLC) PD-L1 testing is now routinely being performed in many diagnostic laboratories as either a complimentary test or a companion diagnostic (CDx) test for 1’ and 2’ line treatment with immune therapy.
As for all IHC assays, PD-L1 is an assay influenced by multiple parameters and the final result will be highly dependent on the choice and performance of these parameters. In addition, no profound test performance characteristics including identification of reliable positive and negative controls have been identified for PD-L1 IHC assays, which complicates the validation of IHC assays for the laboratories. In this context it has to be emphasized, that the challenge for PD-L1 IHC assay is more difficult compared to other similar biomarkers. For HER2 IHC, the validation process can be supported by in situ hybridization methods serving as reference for the HER2 IHC test results. This is not applicable for PD-L1 IHC, as no second method for the PD-L1 status exists. At present, the best solution for diagnostic laboratories is the use of CDx assays, which have been validated by the IHC system providers. However, access to a specific IHC stainer platform, is a basic requirement for the laboratories performing the PD-L1 CDx assay and this is limiting factor and posing a need to use alternative and laboratory developed (LD) assays for PD-L1.
Data generated from the NordiQC IHC proficiency scheme focusing on HER2 IHC tests in breast carcinoma, has in 25 consecutive proficiency tests with > 300 laboratories participating revealed an inferior performance LD assays compared to CDxs.
In addition, focus on interpretation of the PD-L1 tests must be addressed. In this aspect introduction and training how to interpret clinical relevant cut-offs is highly relevant. For PD-L1 the interpretation is challenged by many obstacles as type of cells being positive, number of cells and a heterogenous staining pattern.
In order to evaluate “Precision Testing” for “Precision Medicine” with immune therapy in NSCLC, NordiQC initiated a new Companion module focusing on PD-L1 IHC. The module will address the precision of PD-L1 testing evaluating the analytical performance of PD-L1 IHC assays used by the laboratories and also the concordance level of interpretation among the participants
These data from the NordiQC Companion module Run C1 is being published by end april 2017 will be presented and discussed.
NordiQC – seminal results during 15 years
Immunohistochemistry (IHC) is a routinely applied assay in surgical and clinical pathology, and essential in the diagnosis and sub-classification of many neoplastic lesions. Despite being extensively used for more than 40 years, lack of standardization and reproducibility is a huge challenge. In order to evaluate the level of inter-laboratory consistency and precision of IHC mainly focusing on the analytical part, Nordic immunohistochemical Quality Control (NordiQC) was established in 2003. In total more than 40.000 IHC slides and 97 different IHC markers have been evaluated in the period 2003-2017. In each assessment run 15-500 laboratories have participated. For each of the markers evaluated, focus has been addressed on the technical performance of the IHC assay and the calibration of the assay to fit-for-purpose. Hereby it has been possible to identify best practice protocols and central protocol parameters to obtain sufficient and optimal results but also allowed a systematic identification of causes for insufficient and poor results. The presentation will review most central observations and lessons to be applied for IHC external quality control.
Søren Nielsen is senior biomedical scientist and project coordinator at Laboratory for Immunohistochemistry/R&D, Institute of Pathology, Aalborg University Hospital, Denmark, where he has worked within immunohistochemistry for more than 20 years. He is scheme manager of Nordic immunohistochemical Quality Control (NordiQC) initiated in 1998 and established as a professional organization in 2003. He functions as assessor and data analyst in the NordiQC general module, breast module and HER-2 ISH module. He is a regular lecturer and organizer of national and international immunohistochemical workshops, particularly in the field of protocol optimization and standardisation.
He is author and co-author of more than 30 scientific papers and several book chapters based on immunohistochemical studies.
Søren Nielsen is board member of the International Society for Immunohistochemistry and Molecular Morphology, trustee of the Biological Stain Commission and member of the editorial board of more international journals.
- Cheung CC, D’Arrigo C, Dietel M, Francis GD, Fulton R, Gilks CB, Hall JA, Hornick JL, Ibrahim M, Marchetti A, Miller K, van Krieken JH, Nielsen S, Swanson PE, Taylor CR, Vyberg M, Zhou X, Torlakovic EE; From the International Society for Immunohistochemistry and Molecular Morphology (ISIMM) and International Quality Network for Pathology (IQN Path). Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine: Part 4: Tissue Tools for Quality Assurance in Immunohistochemistry. Appl Immunohistochem Mol Morphol. 2016 Dec 9. [Epub ahead of print]
- Cheung CC, D’Arrigo C, Dietel M, Francis GD, Gilks CB, Hall JA, Hornick JL, Ibrahim M, Marchetti A, Miller K, van Krieken JH, Nielsen S, Swanson PE, Taylor CR, Vyberg M, Zhou X, Torlakovic EE; From the International Society for Immunohistochemistry and Molecular Morphology (ISIMM) and International Quality Network for Pathology (IQN Path).. Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine: Part 1: Fit-for-Purpose Approach to Classification of Clinical Immunohistochemistry Biomarkers. Appl Immunohistochem Mol Morphol. 2017 Jan;25(1):4-11.
- Nielsen SL, Nielsen S, Vyberg M. Digital Image Analysis of HER2 Immunostained Gastric and Gastroesophageal Junction Adenocarcinomas. Appl Immunohistochem Mol. Morphol. 2016 Oct 31. [Epub ahead of print] PubMed PMID: 27801737.Nielsen SL, Nielsen S, Vyberg M. Digital Image Analysis of HER2 Immunostained Gastric and Gastroesophageal Junction Adenocarcinomas. Appl Immunohistochem Mol Morphol. 2016 Oct 31. [Epub ahead of print]
- Røge R, Riber-Hansen R, Nielsen S, Vyberg M. Proliferation assessment in breast carcinomas using digital image analysis based on virtual Ki67/cytokeratin double staining. Breast Cancer Res Treat. 2016 Jul;158(1):11-9.
- Vyberg M, Nielsen S, Røge R, Sheppard B, Ranger-Moore J, Walk E, Gartemann J, Rohr UP, Teichgräber V. Immunohistochemical expression of HER2 in breast cancer: socioeconomic impact of inaccurate tests. BMC Health Serv Res. 2015 Aug 29;15:352.
- Vyberg M, Nielsen S. Proficiency testing in immunohistochemistry-experiences from Nordic Immunohistochemical Quality Control (NordiQC). Virchows Arch. 2016 Jan;468(1):19-29.
- Nielsen S. External quality assessment for immunohistochemistry: experiences from NordiQC. Biotech Histochem. 2015 Jul;90(5):331-40
- Torlakovic EE, Nielsen S, Vyberg M, Taylor CR. Getting controls under control: the time is now for immunohistochemistry. J Clin Pathol. 2015 Nov;68(11):879-82
- Torlakovic EE, Nielsen S, Francis G, Garratt J, Gilks B, Goldsmith JD, Hornick JL, Hyjek E, Ibrahim M, Miller K, Petcu E, Swanson PE, Zhou X, Taylor CR, Vyberg M.Standardization of positive controls in diagnostic immunohistochemistry: recommendations from the International Ad Hoc Expert Committee. Appl Immunohistochem Mol Morphol. 2015 Jan;23(1):1-18.