Immunohistochemistry as an assay

Dear Editor,

The National Society for Histotechnology (NSH) was delighted to see the editorial entitled ‘Immunohistochemistry Should Be Regulated as an Assay’ by B.J. Magnani and C. Taylor published in the Archives of Pathology & Laboratory Medicine [1]. Since its inception as a diagnostic tool in anatomic pathology, immunohistochemistry (IHC) has been referred to as a ‘stain.’ This notion is an offshoot of traditional histochemical techniques that supplemented morphological interpretation and is antiquated terminology. A number of consensus guideline documents, from a number of organizations, refer to IHC as an assay [2–4]. While perhaps valid in the early days, IHC’s role changed significantly in the 1990’s with the development of companion diagnostics [1]. IHC testing has developed into an assay where both qualitative and quantitative information are critical to the result. However, while the methods, application and reporting of IHC tests have changed, quality assurance and quality control methods and their regulation have not [1,5]. IHC test quality assurance is grounded in subjective pass/fail interpretation based on non-standardized control tissues that are insensitive and irreproducible. There is a need to implement more rigorous quality control standards and metrics to better understand the total test concept and mitigate the challenges faced during test failure [5,6]. The major obstacle has been the lack of appropriate tools to assess assay performance spanning pre-analytical to post analytical methodology. The use of the term ‘stain’ belies the complexity of IHC. Immunohistochemistry is extremely complex and similar to clinical immunoassays, using similar antibodies and reagents, detecting similar protein targets and governed by similar immunological and biochemical principles [6,7]. What is strikingly different is the medium in which the assay is performed. Clinical assays operate in a liquid substrate environment while IHC is performed on solid or semi-solid substrate that is poorly defined and inconsistent in its behavior and properties. The application of robust IHC calibrator technology, now available, can only help clarify the nuances of the complex relationship between the phases of the Total Test and change the paradigm from a ‘stain’ to an assay. Clearly, increasing the rigor with analytical standardization will help address both interpretive and technical errors [5]. While patient sample interpretation may be the purview of the pathologist, it is the histologist who performs thousands if not hundreds of thousands of IHC tests on multiple pieces of complex equipment as well as managing all the samples, controls and ancillary materials with the added responsibility of documenting every step. NSH strongly supports the notion that immunohistochemistry should be considered an assay and not a ‘stain.’ Given the complexity of performing clinical IHC testing, the number of tests performed annually and the importance of the results to patient care, NSH firmly believes that it is time to take the steps necessary to improve the quality of clinical IHC practice based on the principles set forth by Magnani and Taylor. In addition, NSH strongly feels that histology professionals, as the laboratory personnel performing these assays, need to be directly involved in the future development of quality assurance tools and regulatory compliance standards. We look forward to entering into the discussion with stakeholders in order to provide the best possible care to the patients we all serve.

Board of Directors, National Society for Histotechnology

Michelle Bell, HT (ASCP) QIHC ^cm

Milestone Medical

ORCID: 0009-0003-0109-0263

Luis Chiriboga, PhD, HT (ASCP) QIHC

NYU Grossman School of Medicine

ORCID: 0000-0002-2028-6873

Elizabeth Chlipala, BS, HTL (ASCP) QIHC

Premier Laboratory, LLC

ORCID: 0000-0002-2194-7645

Colleen Forster, BS HT (ASCP) QIHC (ASCP)

University of Minnesota

ORCID: 0000-0001-5593-882X

Jeremy Johnston, BS, HT (ASCP), QIHC (ASCP)

Virginia Mason Franciscan Health

ORCID: 0009-0002-1770-2706

Jerry Santiago, PhD, HTL (ASCP) QIHC

Professor of Histology/Program Director HT Florida State College at Jacksonville

ORCID: 0009-0003-5132-6967

Dawn Schneider, HT (ASCP)

Aspirus Health

ORCID: 0009-0003-0368-7936

Shameika J. Winfrey, PBT, HT (ASCP)

Baylor University Medical Center - Dallas

ORCID: 0009-0002-9332-0320

IHC Committee

Brenda L Schlosser, HTL, QIHC

Advanced Staining Field Applications Specialist for Leica Biosystems

ORCID: 0009-0005-5541-5101

Clare Thornton HTL (ASCP) ^CM, QIHC (ASCP) ^CM

Dahl Chase Diagnostic Services

ORCID: 0009-0009-4276-5726

Elba G. Vidal, MHA, HTL (ASCP) ^CM, QIHC (ASCP) ^CM

University of Maryland Medical Center

ORCID: 0009-0006-5923-6132