IHC Staining and Molecular Biomarkers

Cancer is a major cause of mortality worldwide, and the evaluation of predictive and prognostic markers is crucial in its pathologic assessment. Immunohistochemistry (IHC) is commonly used to evaluate biomarker status and guide the use of specific therapies. However, with over 41,800 publications on IHC biomarkers and 27,300 publications on cancer immunohistochemical markers indexed in PubMed as of 2023, it is a challenge to gain an overview on IHC staining possibilities.

When interpreting molecular biomarkers, we are faced with the same problem. And since, on the image analysis side, we get into contact with a wide variety of markers in a wide variety of cases, we started to create an overview of immunohistochemical markers. Naturally, this overview is never complete and only a drop in the ocean.

In terms of image analysis for IHC biomarkers, check out the following MIKAIA University application notes:

• IHC Profiler – Assessing New IHC Assay Using Multi-organ TMA
• IHC Cell Detection
• Spatial Clustering of IHC+ cells
• …and further arcticles with the “IHC” tag

Marker	Histology	Cell type	Function	Localisation
CD1	1	Antigen presenting cells	Mediate presentation of endogenous and foreign lipids on cell surface for recognition by T cell receptors	Surface protein
CD2		T cells, NK cells, dendritic cells, thymocytes	Mediates adhesion between T cells and antigen presenting cells	Surface protein
CD3	2	T cells	Main component of the T cell antigen receptor	Cytoplasmic positivity in immature T cells   Complete and membranous positivity in mature T cells
CD4	3	T helper cell	T cell activation	Surface protein
CD6		Mature T cells, B cell subset, NK cells, high levels on mature thymocytes	Essential for stable contact between T cells and antigen presenting cells, which leads to T cell proliferation	Surface protein
CD7	4	Thymocytes, mature T cells, NK cells	T cell B cell interaction in early lymphoid development	Surface protein
CD8	5	Cytotoxic T cells	Recognize antigens displayed by an antigen presenting cell	Surface protein
CD9	6	Pre B cells, B cell subset, activated T cells, basophils, eosinophils, monocytes, thrombocytes, Brain, cardiac muscle, vascular smooth muscle	Mediates adhesion, migration, signal transduction	Surface protein
CD10	7	B and T progenitor cells	Degradation of small peptides	Surface protein
CD11a	8	B- and T-lymphocytes, monocytes, macrophages, neutrophils, basophils, and eosinophils	Binds to CD18 adhesion molecule, signal transduction	Surface protein
CD11b	9	Granulocytes, monocytes/ macrophages, and NK cells, and subsets of B- and T-cells	Adhesion molecule	Surface protein
CD11c		Expression is high in monocytes/ macrophages, NK cells, hairy cells   Expression is moderate in granulocytes, and weak in lymphocyte subsets	Adhesion molecule	Surface protein
CD14	10	Macrophages / monocytes, Langerhans cells, dendritic cells, B cells and granulocytes	Detects antigenic molecules	Surface protein
CD15		Monocytes, granulocytes	Mediates phagocytosis   Diagnosis of Hodgkin lymphoma	A carbohydrate (not a protein) on the cell surface   membranous, diffuse cytoplasmic or Golgi staining in Hodgkin lymphoma
CD16		NK cells, granulocytes, monocytes / macrophages, T cells	Signal transduction	Surface protein
CD18	11	Neutrophils, basophils macrophages, monocytes, NK cells	Important for adhesion and signaling in the hematopoietic system Forms the beta 2 chain of CD11a-c enabling cell adhesion.	Surface protein
CD19		B cells	Regulates B cell development, activation and differentiation	Surface protein
CD20	12	B cells	Activation of B cells	Surface protein
CD21	13	Mature B-cells and follicular dendritic cells	Part of the B-cell co- receptor complex   Interacts with CD19 and CD81 B-cell activation and maturation	Surface protein
CD22		Mature B-cells	Regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases	Surface protein
CD23	14	Mature B cells, activated macrophages, eosinophils, follicular dendritic cells	Mediates multiple immunologic functions	Surface protein
CD24	15	B cells, granulozytes	Cell adhesion	Surface protein
CD25		T regulatory cells	Immunoregulatory functions	Surface protein
CD27		B, T and NK cells	Member of the TNF- receptor superfamily Required for generation and long- term maintenance of T cell immunity   Binds to CD70	Surface protein
CD28	16	T cells	T cell activation and survival   Binds to CD80 and CD86	Surface protein
CD29		Leukocytes	Cell adhesion, immune response   Interacts with CD49a	Surface protein
CD30	17	Activated T- and B-cells, monocytes, Reed-Sternberg cells and T-cell lymphomas	Regulates lymphocyte proliferation and cell death. Critical role in the pathophysiology of Hodgkin’s disease and other CD30+ lymphomas	Surface protein
CD31	18	Monocytes, platelets, endothelial cells.	Cell adhesion, immune cell transmigration and angiogenesis	Surface protein
CD33	19	Cells of myeloid lineage	Lectin activity and adhesion. A receptor that inhibits the proliferation of normal, leukemic myeloid and lymphoid cells	Surface protein
CD34	20	Hematopoietic stem cells and progenitors, capillary endothelial cells.	Ligand for CD62L   Major vascular selectin ligand – necessary for the first step of cell migration	Surface protein
CD35	21	Erythrocytes,  monocytes, granulocytes, neutrophils, eosinophils, splenic follicular dendritic cells.	Receptor for complement components C3b and C4b. Mediates adhesion and phagocytosis.	Surface protein
CD36	22	Found on many cells and tissues; Platelets, monocytes, endothelial cells	Involved in signal transduction in immunity; Adhesion molecule of thrombocytes; involved in recognition and phagocytosis of apoptotic cells.	Surface protein
CD37		Mature B-cells and myeloid cells.	Signal transduction. Regulates T-cell proliferation. Involved in the spatial organization of B-cell plasma membrane.	Surface protein
CD38	23	T-cells, B-cells, plasma cells and NK cells.	Functions in cell adhesion, signal transduction and calcium signaling	Surface protein
CD39	24	Activated lymphoid cells	Involved in the cellular signaling that regulates adhesion and adenosine- mediated immunosuppression	Surface protein
CD44	25	Ubiquitously expressed on many types of cells of lymphohematopoietic origin, including erythrocytes, T and B cells, NK cells, macrophages, Kupffer cells, dendritic cells and granulocytes	Cell adhesion	Surface protein
CD45	26	Leucocytes	Supports T cell activation and signal transduction	Surface protein
CD68	27	Monocytes, macrophages	Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites	Surface protein
ER/PR	28	Estrogen Receptor and Progesterone Receptor	ER and PR status should be tested on breast tumor	Nuclear
FoxP3	29	Regulatory T cells (Treg)	Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells	Nuclear
HLA-DR	30	Antigen-presenting cells	Presents peptide antigens	Surface protein
Iba-1	31	Microglia/macrophage- specific calcium-binding protein	Involved with membrane ruffling and phagocytosis in activated microglia	Surface protein
Ki-67	32	Proliferation marker	Prevents aggregation of mitotic chromosomes	Nuclear
MLH1 MSH2 MSH6 PMS2	33	Ubiquitously expressed	DNA mismatch repair proteins   Associated with hereditary nonpolyposis colorectal cancer	Nuclear
NKp46	34	NK cells	NK cell-activating receptor that is involved in the elimination of target cells	Surface protein
p53	35	Tumor suppressor protein	Promotes cell cycle arrest to allow DNA repair and/or apoptosis to prevent the propagation of cells with serious DNA damage.   Most frequently mutated gene (>50%) in human cancer	Nuclear
PD-1 [CD279]	36	Activated T cells, NK cells, B lymphocytes, macrophages, dendritic cells, monocytes	Inhibits immune responses and promotes self- tolerance through modulating the activity of T-cells	Surface protein
PD-L1	37	Macrophages, some activated T cells and B cells, DCs, epithelial cells	Co-inhibitory factor of the immune response	Surface protein
TCR		T cell receptor	Functions in recognizing bound antigens derived from a potentially harmful pathogen and elicits a distinct and critical response	Surface protein
TER119		Erythrocytes	Associates with glycophorin A	Surface protein

Are you missing a certain marker or histology? Please leave a comment or write us an e-mail ! We’ll be happy to add that to the list.

Source of feature image: https://en.wikipedia.org/wiki/Immunohistochemistry#/media/File:Main_staining_patterns_on_immunohistochemistry.jpg

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