CD38 (MSVA-038R)

CD38 (cluster of differentiation 38), also termed cyclic ADP ribose hydrolase, is coded by the CD38 gene on chromosome 4p15. CD38 is a transmembrane glycoprotein with a large bifunctional extracellular catalytic domain which is predominantly expressed in various types of leukocytes. In these cells, CD38 exerts diverse functions as a receptor and as an enzyme. It is involved in the regulation of cell adhesion, migration, proliferation, intracellular signal transduction, metabolic reprogramming, modulation of the cell microenvironment. Accordingly, CD38 plays a pivotal role in inflammation and immunity. CD38 binding to its ligand CD31, mediates adhesion between leukocytes and the endothelial wall, and promotes transmigration, activation as well as proliferation. CD38 further regulates the migration of dendritic cell (DC) precursors from blood to peripheral sites, and of mature DCs to lymph nodes. The extracellular enzymatic domain of CD38 is required to synthesize the second messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) that are both essential for intracellular calcium homeostasis. CD38 can be highly overexpressed in hematological neoplasms, especially in plasmacytoma. CD38 thus serves as a target for monoclonal antibodies such as daratumumab or isatuximab which are successfully applied in malignant myeloma and also in the treatment of asthma.

Images describing the CD38 staining pattern in normal tissues obtained by the antibody MSVA-038R are shown in our “Normal Tissue Gallery”.

A membranous CD38 expression occurs in various subtypes of inflammatory cells, endothelial cells at selected locations as well as in the epithelium of the prostate and of seminal vesicles.

RNA and protein expression data of CD38 findings are also described in the Human Protein Atlas (Tissue expression CD38).

Positive control = Prostate: A strong CD38 positivity of epithelial cells should be seen.

Negative control = Colon: Epithelial cells must be CD38 negative.

Normal tissue gallery

Cancer tissue gallery

No data available at the moment

IHC users have different preferences on how the stains should look like. Some prefer high staining intensity of the target stain and even accept some background. Others favor absolute specificity and lighter target stains. Factors that invariably lead to more intense staining include higher concentration of the antibody and visualization tools, longer incubation time, higher temperature during incubation, higher temperature and longer duration of the heat induced epitope retrieval (slide pretreatment). The impact of the pH during slide pretreatment has variable effects and depends on the antibody and the target protein.

All images and data shown here and in our image galleries are obtained by the manual protocol described below. Other protocols resulting in equivalent staining are described as well.

Manual protocol

Freshly cut sections should be used (less than 10 days between cutting and staining). Heat-induced antigen retrieval for 5 minutes in an autoclave at 121°C in pH 7,8 Target Retrieval Solution buffer. Apply MSVA-038R at a dilution of 1:50 at 37°C for 60 minutes. Visualization of bound antibody by the EnVision Kit (Dako, Agilent) according to the manufacturer’s directions.

• The prognostic role of CD38 expression in hematological neoplasms is of further interest.
• The prognostic role of CD38 expression in prostate cancer is unknown.
• The prevalence of CD38 expression in hematological malignancies is unclear.
• The potential therapeutic benefit of anti CD38 antibodies (or derivatives) for epithelial neoplasms is unknown.

There are two ways how the specificity of antibodies can be documented for immunohistochemistry on formalin fixed tissues. These are: 1. Comparison with a second independent method for target expression measurement across a large number of different tissue types (orthogonal strategy), and 2. Comparison with one or several independent antibodies for the same target and showing that all positive staining results are also seen with other antibodies for the same target (independent antibody strategy). 

Orthogonal validation: For the antibody MSVA-038R specificity is suggested by the strong concordance of the immunostaining data with data from three independent RNA screening studies, including the Human Protein Atlas (HPA) RNA-seq tissue dataset, the FANTOM5 project, and the Genotype-Tissue Expression (GTEx) project, which are all summarized in the Human Protein Atlas (Tissue expression CD38). In agreement with MSVA-038R immunostaining data, RNA expression predominated in seminal vesicle, prostate, bone marrow & lymphoid tissues as well as in tissues that are known for a high content of inflammatory cells such as the gastrointestinal tract. The high CD38 RNA expression in skeletal muscle is the only RNA finding which is not in line with the MSVA-038R immunostaining data. 

Comparison of antibodies: True expression of CD38 in all cell types with CD38 positivity by MSVA-038R is corroborated by an identical staining obtained by a commercially available independent second antibody (termed “validation antibody”). As this second antibody did also not stain skeletal muscle, it appears possible that RNA expression analysis may have involved highly vascularized skeletal muscle containing many intravascular leucocytes or else a contamination by adjacent inflammation or lymphatic tissue.

Normal tissue gallery