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Synonyms = ADP Ribosyl Cyclase 1; cADP-ribose Hydrolase 1; CD38H; NAD(+) Nucleosidase; NIM-R5 Antigen; p45; T10 Acute Lymphoblastic Leukemia Cells Antigen

Antibody type = Recombinant Rabbit monoclonal / IgG

Clone = MSVA-038R

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

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

Cellular localization = Membrane

Reactivity = Human

 

 

Application = Immunohistochemistry
Dilution = 1:50 – 1:100
Intended Use = Research Use Only

Relevance of Antibody

CD38 is a Pivotal molecule for immunity and calcium homeostasis.

Biology Behind

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.

Staining Pattern in Normal Tissues

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

Brain Cerebrum Negative.
Cerebellum Negative.
Endocrine Tissues Thyroid Negative.
Parathyroid Negative.
Adrenal gland Negative.
Pituitary gland Weak to moderate CD38 staining of endothelial cells of small blood vessels of the adenohypophysis.
Respiratory system Respiratory epithelium A weak membranous CD38 staining occurs in a fraction of respiratory epithelial cells.
Lung Negative.
Gastrointestinal Tract Salivary glands Negative.
Esophagus All epithelial cells are CD38 negative.
Stomach Negative. CD38 positive inflammatory cells do regularly occur.
Duodenum Negative. CD38 positive inflammatory cells do regularly occur.
Small intestine Negative. CD38 positive inflammatory cells do regularly occur.
Appendix Negative. CD38 positive inflammatory cells do regularly occur.
Colon Negative. CD38 positive inflammatory cells do regularly occur.
Rectum Negative. CD38 positive inflammatory cells do regularly occur.
Liver Few CD38 positive monocytic cells.
Gallbladder Negative.
Pancreas Negative.
Genitourinary Kidney Negative.
Urothelium Urothelial cells are CD38 negative. Some inflammatory cells show distinct staining.
Male genital Prostate Strong membranous CD38 staining of most epithelial cells. Staining is weaker or absent in basal cells.
Seminal vesicles Strong membranous CD38 staining of epithelial cells.
Testis Negative.
Epididymis Negative.
Female genital Breast Negative.
Uterus, myometrium Negative.
Uterus, ectocervix Negative.
Uterus endocervix Negative.
Uterus, endometrium Negative.
Fallopian Tube Negative.
Ovary Negative.
Placenta early Negative.
Placenta mature Negative.
Amnion Negative.
Chorion Negative.
Skin Epidermis Negative.
Sebaceous glands Negative.
Muscle/connective tissue Heart muscle Negative.
Skeletal muscle Negative.
Smooth muscle Negative.
Vessel walls Negative.
Fat Negative.
Stroma Negative.
Endothelium CD38 staining can occur in specific organs (adenohypophysis)
Bone marrow/lymphoid tissue Bone marrow Negative.
Lymph node Distinct CD38 staining of a subset of lympho-/ histiocytic cells.
Spleen Distinct CD38 staining of a subset of lympho-/ histiocytic cells.
Thymus Distinct CD38 staining of a subset of lympho-/ histiocytic cells. CD38 staining intensity is highest in cortical thymocytes.
Tonsil Distinct CD38 staining of a subset of lympho-/ histiocytic cells. CD38 staining is particularly prominent in cells (plasma cells?) located near the tonsil crypts.
Remarks A distinct CD38 staining is seen in a subset of lympho-/ histiocytic cells. Such cells can occur in virtually all organs.

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

Staining Pattern in Relevant Tumor Types

A positive CD38 immunostaining can be seen in most plasmacytomas and in various other hematological malignancies. CD38 expression also occurs in a fraction of prostatic adenocarcinomas and can – more rarely – also in other epithelial tumors.

The TCGA findings on CD38 RNA expression in different tumor categories have been summarized in the Human Protein Atlas.

 

 

Cancer tissue gallery

Compatibility of Antibodies

No data available at the moment

Protocol Recommendations

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.

Potential Research Applications

  • 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.

Evidence for Antibody Specificity in IHC

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