Glypican 3 Monoclonal Antibody (ZM138)

Product Specific Information

This product is diluted and in a ready-to-use formulation.

A recommended positive control tissue for this product is HCC, however positive controls are not limited to this tissue type.

The primary antibody is intended for laboratory professional use in the detection of the corresponding protein in formalin-fixed, paraffin-embedded tissue stained in manual qualitative immunohistochemistry (IHC) testing. This antibody is intended to be used after the primary diagnosis of tumor has been made by conventional histopathology using non-immunological histochemical stains.

Glypican-3 (GPC3) is a glycosylphosphatidyl inositol-anchored membrane protein, which may also be found in a secreted form. Anti-GPC3 has been identified as a useful tumor marker for the diagnosis of hepatocellular carcinoma (HCC), hepatoblastoma, melanoma, testicular germ cell tumors, and Wilm’s tumor. In patients with HCC, GPC3 is overexpressed in neoplastic liver tissue and elevated in serum, but is undetectable in normal liver, benign liver, and the serum of healthy donors. GPC3 expression is also found to be higher in HCC liver tissue than in cirrhotic liver or liver with focal lesions such as dysplastic nodules and areas of hepatic adenoma (HA) with malignant transformation. In the context of testicular germ cell tumors, GPC3 expression is up regulated in certain histologic subtypes, specifically yolk sac tumors and choriocarcinoma. A high level of GPC3 expression is also found in some types of embryonal tumors, such as Wilm’s tumor and hepatoblastoma, with a low or undetectable expression in normal adjacent tissue.

Antibody is used with formalin-fixed and paraffin-embedded sections. Pretreatment of deparaffinized tissue with heat-induced epitope retrieval or enzymatic retrieval is recommended. In general, immunohistochemical (IHC) staining techniques allow for the visualization of antigens via the sequential application of a specific antibody to the antigen (primary antibody), a secondary antibody to the primary antibody (link antibody), an enzyme complex and a chromogenic substrate with interposed washing steps. The enzymatic activation of the chromogen results in a visible reaction product at the antigen site. Results are interpreted using a light microscope and aid in the differential diagnosis of pathophysiological processes, which may or may not be associated with a particular antigen.

A positive tissue control must be run with every staining procedure performed. This tissue may contain both positive and negative staining cells or tissue components and serve as both the positive and negative control tissue. External Positive control materials should be fresh autopsy/biopsy/surgical specimens fixed, processed and embedded as soon as possible in the same manner as the patient sample (s). Positive tissue controls are indicative of correctly prepared tissues and proper staining methods. The tissues used for the external positive control materials should be selected from the patient specimens with well-characterized low levels of the positive target activity that gives weak positive staining. The low level of positivity for external positive controls is designed to ensure detection of subtle changes in the primary antibody sensitivity from instability or problems with the staining methodology. A tissue with weak positive staining is more suitable for optimal quality control and for detecting minor levels of reagent degradation.

Internal or external negative control tissue may be used depending on the guidelines and policies that govern the organization to which the end user belongs to. The variety of cell types present in many tissue sections offers internal negative control sites, but this should be verified by the user. The components that do not stain should demonstrate the absence of specific staining, and provide an indication of non-specific background staining. If specific staining occurs in the negative tissue control sites, results with the patient specimens must be considered invalid.

Target Information

GPC3 is a cell surface proteoglycan that bears heparan sulfate. This protein may be involved in the suppression/modulation of growth in the predominantly mesodermal tissues and organs, and may play a role in the modulation of IGF2 interactions with its receptor and thereby modulate its function. Members of the glypican-related integral membrane proteoglycan family contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol (GPI) linkage. These proteins may play a role in the control of cell division, growth regulation, and tumor predisposition. Deletion mutations in GPC3 are the cause of Simpson-Golabi-Behmel syndrome (SGBS), also known as Simpson dysmorphia syndrome (SDYS). SGBS is a condition characterized by pre- and postnatal overgrowth (gigantism) with visceral and skeletal anomalies.