Should all tumour markers be standardised?
International Standards and International Reference Preparations are available for most tumour markers measured by immunoassay, which improve the accuracy and comparability of assay results. If the benefits of standardisation are clear, should we not be striving to provide standards for all tumour markers?
Confidence in immunoassay results is improved when they are calibrated using an established internationally recognised standard preparation1. Such standards are usually prepared and characterised by expert groups and endorsed by an appropriate governing body, such as the World Health Organisation (WHO) or the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Standardisation initiatives relating to a number of analytes are currently being progressed by working groups of the scientific division of the IFCC.
The between-method agreement of results obtained with different immunoassay methods is often poor, particularly for complex serum tumour markers. The availability and adoption of well-characterised International Standards and Reference Preparations can help to improve this.
A very good example of the benefits of assay standardisation is Prostate Specific Antigen (PSA), the First International Reference Preparation for PSA was introduced in 20012.
The PSA standard was shown to successfully improve agreement in PSA results reported for the same specimen using different methods3. However, although this improvement in comparability helped align the assay results, a survey of the clinical impact of the standardisation showed that it was still desirable to continue to report the specific method when reporting a PSA value4.
The importance of having an International Standard for PSA was recently confirmed in conclusions of a workshop held by the PSA test harmonisation board in December 2014. This group, supported by the US NCCP, reported that “only assays calibrated to the WHO International Standard for Prostate-Specific Antigen shall be used”. The successful introduction and widespread adoption of the WHO 1st IRP for PSA has meant that a replacement standard is now required. The work required to identify and establish the new International Standard is being coordinated by the National Institute for Biological Standards and Controls (NIBSC).
While appropriate International Standards are available for important serum tumour markers such as PSA, AFP, hCG and CEA, there are as yet no such standards for the mucinous tumour markers CA125, CA15-3 and CA19-9. It is interesting to consider why this is the case, as discussed in a recent journal article which explains why these assays should be standardised5. Contributing to such discussion, an investigation by BBI Solutions, undertaken in collaboration with the UK NEQAS unit in Sheffield, has demonstrated the potential utility of purified proteins as calibrants that might be appropriate for use in a standardisation program6 (access results here). To date these programs have not received international backing.
Dr Catharine Sturgeon will be joining BBI Solutions in a webinar to review the utility of these assays and set out the case for an international effort to align manufacturer’s assays. If you would like to understand more about the benefits of creating an international standard for these assays, sign up to attend today.
1 New International Reference Preparation for proteins in human serum. J T Whicher, R F Ritchie, A M Johnson, S Baudner, J Bienvenu, S Blirup-Jensen, et al. Clin. Chem. 1994 40; 6: 934-938
2 NIBSC product information sheet code 96/670
3 Improving the comparability for Prostate Specific Antigen (PSA): Progress and pitfalls. Sturgeon CM and Ellis AR. Clin Chim Acta 2007; 381: 85-92
4 The clinical impact of WHO standardisation of PSA assays. Blanchet JS and Brinkmann T. JMB 2008; 27: 161-168
5 Standardization of tumour markers – priorities identified through external quality assessment Sturgeon C. Scand J Clin Lab Invest, 76 S245: S94–S99
6 Assessment of preparations of the mucin tumour marker antigens on different immunoassay platforms – Is standardisation possible? Egner W, Patel D, White P, Packer S, Jewess P, Murray D AACC poster 2009