Immunohistochemistry Innovations for Diagnosis and Tissue-Based Biomarker Detection
Purpose of Review
Immunohistochemistry is an integral technique for tissue-based diagnostics and biomarker detection with broad worldwide adoption. Advances in core chemistries, antibody design, and automation have ushered unprecedented sensitivity, specificity, and reproducibility in immunohistochemistry assays. As a result, clinical immunohistochemistry assays that utilize dual-color approaches and mutation-specific antibodies provide novel tools in clinical diagnostics that until recently were in the realm of investigational research. This review provides an overview of innovations in clinical immunohistochemistry assays with emphasis on those used for patients with hematopoietic neoplasms.
Advances in clinical-grade immunohistochemistry techniques have allowed labs to develop and validate multiplex assays that improve diagnostic utility—such as CD5/PAX5 and TCF4/CD123 dual-color stains—and have the potential to enhance the specificity of biomarker detection. In addition, the increased availability of immunohistochemistry assays that detect mutant proteins (e.g., BRAF V600E and IDH1 R132H) provides a helpful replacement and/or adjunct for molecular testing. These techniques are highly reproducible, entail reasonable technical and interpretation complexity, and are relatively cost-effective, making them valuable novel tools in modern cancer care.
Multiplex and mutation-specific immunohistochemistry assays represent important innovations that provide improved utility in the context of personalized medicine and targeted therapy.
KeywordsDual immunohistochemistry Multiplex immunohistochemistry Mutation-specific antibody BRAF V600E CD123 IDH1 LEF1 PAX5 TCF4
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.•• Khoury JD, Wang WL, Prieto VG, et al. Validation of immunohistochemical assays for integral biomarkers in the NCI-MATCH EAY131 clinical trial. Clin Cancer Res. 2018;24:521–31 This paper describes in detail principles of immunohistochemistry validation in the context of integral biomarkers used for therapy selection in a large national clinical trial. PubMedGoogle Scholar
- 4.Coons A, Creech H, Jones R. Immunological properties of an antibody containing a fluorescent group. Proc Soc Exp Biol Med. 1941;47:200–2.Google Scholar
- 7.• Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010;134:e48–72 Landmark paper providing guidelines for breast cancer biomarker testing my immunohistochemistry. PubMedGoogle Scholar
- 9.Khogeer H, Rahman H, Jain N, Angelova EA, Yang H, Quesada A, et al. Early T precursor acute lymphoblastic leukaemia/lymphoma shows differential immunophenotypic characteristics including frequent CD33 expression and in vitro response to targeted CD33 therapy. Br J Haematol. 2019.Google Scholar
- 14.Medeiros L, Miranda R. Diagnostic pathology: lymph nodes and extranodal lymphomas. 2017.Google Scholar
- 47.Swerdlow SH. WHO classification of tumours of haematopoietic and lymphoid tissues. 2017.Google Scholar
- 70.Routhier CA, Mochel MC, Lynch K, Dias-Santagata D, Louis DN, Hoang MP. Comparison of 2 monoclonal antibodies for immunohistochemical detection of BRAF V600E mutation in malignant melanoma, pulmonary carcinoma, gastrointestinal carcinoma, thyroid carcinoma, and gliomas. Hum Pathol. 2013;44:2563–70.PubMedGoogle Scholar
- 74.Oh HS, Kwon H, Park S, Kim M, Jeon MJ, Kim TY, et al. Comparison of immunohistochemistry and direct Sanger sequencing for detection of the BRAF(V600E) mutation in thyroid neoplasm. Endocrinol Metab (Seoul). 2018;33:62–9.Google Scholar