The Nordic Immunohistochemical Quality Control (NordiQC) proficiency testing scheme provides a comprehensive quality assessment service, including:
The General module comprises three annual runs with IHC tests for approximately 15 different antigens in formalin-fixed, paraffin-embedded tissues. The markers are selected to cover a broad range of commonly used antibodies as well as selected specialised and newly introduced markers.
The Breast Cancer module comprises one annual run with IHC tests for HER2, estrogen receptor and progesterone receptor.
The Companion module comprises one annual run with IHC tests for PD-L1, CLDN18.2 and FOLR1.
The HER2 ISH module comprises one annual run with in situ hybridisation (ISH) testing for HER2 in breast cancer. The module includes CISH/SISH testing on formalin-fixed, paraffin-embedded tissue sections. FISH is also included, with NordiQC assessing laboratory scoring only.
1. Pathology laboratories enrolled in the scheme participate in an assessment run by staining slides circulated by NordiQC. Unstained slides are only sent to particapants after submission of the relevant staining protocols via the NordiQC website before the announced deadline. Protocols submitted by email or letter are not accepted. Submitted protocols may be edited until the assessment and will be locked thereafter.
2. Only the stains listed for a particular run can be submitted for assessment. If a laboratory does not have an antibody required for detection of a specific epitope, it cannot be replaced by another antibody. This is due to the design of the multi-tissue blocks and the need for a sufficient number of comparable stains to ensure a valid assessment. For the same reason, stains performed with inappropriate or irrelevant antibodies are not assessed.
3. The circulated sections are serial sections cut from multi-tissue blocks containing several anonymised normal and tumour tissues fixed in 10% neutral buffered formalin and embedded in paraffin. NordiQC distributes only medical glass slides containing fixed tissue. The material is certified as non-hazardous, non-contagious and non-infectious and has no commercial value.
The tissues are selected according to the purpose of the immunohistochemical analysis and include clinically relevant and critical expression levels of the target analyte. Expected expression levels are characterised using NordiQC immunohistochemical reference methods. Reference staining is performed at different levels of the multi-tissue blocks to monitor homogeneity and identify potential heterogeneity in the circulated material.
For each epitope, one unstained section is sent to participating laboratories that have submitted the required protocols before the announced deadline. Accompanying letters containing basic information, including the TMA layout, tissues included and submission deadline, are available at www.nordiqc.org. Dates for slide circulation are available in the module overview.
4. Laboratories are requested to stain the slides using their standard protocols. The stains for each epitope should be returned to NordiQC in time for the assessment. In the event of a broken or damaged slide, a replacement may be requested by contacting NordiQC. Documentation of the damage is required, and replacement slides can only be provided if sufficient material is available.
5. All stained slides returned to NordiQC are assessed and graded by the assessor group. In general, the assessment is based on staining intensity and distribution in cells expected to stain, background staining, signs of cross-reactivity, counterstaining and tissue preservation during the staining procedure. Detailed assessment criteria and expected staining results are provided in the general assessment report for each marker.
Each participant slide is assessed by projecting the microscopic image onto a monitor and directly comparing it with the NordiQC reference method, displayed on a second monitor. All reference and circulated slides used for assessment are numbered according to their position in the multi-tissue block. This allows the submitted slide to be compared with the corresponding reference section located as close as possible within the block, thereby minimising the influence of tissue heterogeneity or variation in expected expression. Any identified heterogeneity is taken into account during assessment.
If a participant slide is damaged, lacks critical tissue components or otherwise cannot be reliably assessed, this will be stated in the individual assessment report.
6. Submitted stained slides are retained in the NordiQC archive for documentation purposes for at least five years.
7. Examples of optimal and suboptimal staining results are presented in the general assessment reports for each epitope. Among protocols producing optimal results, selected protocols are displayed anonymously on the NordiQC website as recommended protocols. These are selected to represent a range of antibodies and staining platforms. Please note that use of these protocols does not replace the need for local validation.
8. Individual NordiQC assessment results are available on the website after login. In cases of borderline or poor staining, recommendations for protocol optimisation are provided. Comments may also be provided for good staining results, for example in cases of excessive counterstaining.
9. Laboratory proficiency testing through NordiQC is restricted to scheduled assessment runs. Due to limitations in staffing and available material, individual proficiency tests cannot be offered outside the scheduled runs.
Provided that an appropriate antibody is used, each stain is marked as optimal, good, borderline or poor.
In case of insufficient (borderline or poor) assessment results, the laboratory may request a reevaluation of the original stain. NordiQC will review the submitted stain, typically within 2–3 weeks, and may provide supplementary documentation if relevant.
Reassessment based on a new stain: If a participant wishes to document improvement, for example after correcting an error or modifying the staining protocol, reassessment on a new slide may be requested. This is typically offered two runs later. To receive a new slide, the participant must submit a new protocol before the deadline for the run in which the reassessment will be performed.
The unstained slides are sent together with the material for a future run (typically two runs later), and the resulting stains are assessed at the assessor meeting. Due to limited capacity, reassessment can only be offered when remaining sufficient material is available. It is limited to one reassessment per test, and is available only for tests in the General and Breast Cancer modules.