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Applications of IHC for Oncology Research

Apr 15, 2021 11:00:00 AM / by Champions Oncology

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Immunohistochemistry (IHC) is one of the oldest and widely used diagnostic techniques that continues to be a valuable tool for immuno-oncology research. IHC is a method for visualizing the tissue localization of specific antigens and has evolved since its development in the 1940s[1]. This method has been an essential diagnostic tool for oncology because it enables pathologists to determine the histological grade of a tumor, which is a critical parameter for predicting the prognosis of tumors and determining the best treatment options. IHC is dependent on the skilled preparation and staining of thin tissue sections that are read by diagnostic pathologists or research scientists.

IHC is based on antibody-mediated detection of specific molecules within a tissue section. Fluorescent dyes are conjugated directly to primary antibodies that bind to a specific target, or unlabeled primary antibodies can be detected with fluorescently labeled secondary antibodies that bind to conserved regions of the primary antibody. Most labels are fluorescent dyes, also known as fluorochromes, that emit light at different wavelengths and can be used in different combinations in the same sample, so long as the excitation and emission wavelengths do not overlap. IHC staining can also be done with peroxidase or alkaline phosphates as well as radioactive labels. A primary objective of IHC is to stain a tissue sample with minimal damage to keep tissue, cellular, and subcellular structures intact and prevent alteration of molecules being stained.

IHC is a valuable tool for preclinical immune-oncology research and has several applications highlighted below.

 

Diagnostic Advances

Progress has been made in cancer diagnosis with the advancement of modern IHC methods, and this has directly improved treatment selection and patient outcomes. Coupled with personalized cancer genomics, IHC can be used to identify subtypes of tumors in a patient that may respond to different molecular inhibitors or adoptive cell therapies[2]. These diagnostic breakthroughs have identified new molecular targets for treatment and have reduced likelihoods of refractory responses and relapses[3]. This coupled approach has also been valuable for monitoring treatment of tumors that express high levels of hormone receptors, such as breast and prostate cancer[4, 5].

 

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Biomarker Detection

Recent advances in the molecular characterization of tumors have defined biomarker panels for specific tumor types, and this has been translated into IHC protocols that can evaluate pharmacodynamics of experimental biologics like immune checkpoint inhibitors that target PD-1 and PD-L1[6]. Biomarker detection has been aided by improvements in digital pathology and quantitative tissue analysis[7]. These analyses can be carried out on both solid tumor sections as well as liquid biopsies from hematologic malignancies. Semi-automated IHC methods have been instrumental to pharmacodynamic biomarker analysis of tissue biopsies that monitor apoptosis or protein turnover under different treatment regimens[8]. These advances in biomarker profiling and IHC are critical to immune-oncology research that uses in vivo models to test the efficacy of novel molecular or cell-based treatments on different tumor types, including well-characterized tumor cell lines and patient-derived xenografts. Many drug and biologic candidates do not proceed to clinical trial because of poor efficacy or undesirable toxicity revealed by these studies, due in part to insights gained from IHC studies.

 

IHC continues to advance with improvements in digital imaging and artificial intelligence-based algorithms applied to slide reading and is being coupled with cellular-level sequence analysis to further deepen our understanding of tumor pathology and identify potential targetable biomarkers.

 

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1. Coons AH, Kalpan MH. Localization antigens in tissue cells. Improvements in a method for the detection of antigen by means of fluorescent antibody. J Exp Med. 1950; 91:1–13.

2. Prigge ES, Arbyn M, et al. Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systemic review and meta-analysis. Int J. of Cancer. 2017; 140(5): 1186-1198.

3. Khan K, Rata M, et al. Functional imaging and circulating biomarkers of response to regrafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study. Gut. 2018; 67(8); 1484-1492.

4. Sinn HP; Scheeweiss A, et al Comparison of immunohistochemistry with PCR for assessment of ER, PR and Ki-67 and prediction of pathological complete response in breast cancer. BMC Cancer. 2017; 17(1):1-10.

5. van der Toom EE, Axelrod HD, de la Rosette JJ, de Reijke TM, Pienta KJ, Valkenburg KC. Prostate-specific markers to identify rare prostate cancer cells in liquid biopsies. Nat Rev Urol. 2019;16(1):7-22.

6. Paré L, Pascual T, et al. Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types. Ann Oncol. 2018; 29:2121–8. 5

7. Ghaznavi F, Evans A, Madabhushi A. Digital imaging in pathology: whole-slide imaging and beyond. Annu Rev Pathol. 2013; 8:331–359.

8. Shinde V, Burke KE, et al. Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology. Vet. Pathol. 2013; 51(1); doi.org/10.1177/0300985813511124.

 

 

Tags: IHC