GSTP1 (MSVA-685R)

Glutathione S-Transferase Pi1 (GSTP1) is a 23 kDa enzyme protein which is coded by the GSTP1 gene at chromosome 11q13.2 and belongs to the glutathione S-transferase (GST) family of enzymes that catalyze the conjugation of glutathione to a variety of electrophilic compounds. This activity is crucial for the detoxification of endogenous and exogenous carcinogens, oxidative stress products and drugs, thereby protecting cells from oxidative damage and mutagenesis. According to its critical role, GSTP1 is ubiquitously expressed in human cells. It is particularly abundant in epithelial cells. GSTP1 polymorphisms have been associated with altered susceptibility to various cancer types, but also other diseases such as non-alcoholic fatty liver. Accordingly, GSTP1 knockout mice have shown increased sensitivity to environmental carcinogens, oxidative stress, and inflammation. GSTP1 dysregulation plays a significant role in cancer development and progression. Overexpression of GSTP1 can contribute to resistance to chemotherapy by detoxifying anticancer drugs. Decreased GSTP1 activity or expression, often due to epigenetic silencing, can heighten vulnerability to carcinogenic damage and support tumor progression through an increased rate of DNA mutations. Cancer studies by IHC have described an unfavorable prognostic impact of both reduced and increased GSTP1 expression and suggested a predictive role of high expression for chemo-resistance. GSTP1 is a potential therapeutic target for cancer and other diseases. Inhibitors of GSTP1, such as ezatiostat and others are under clinical investigation as sensitizers to chemotherapy or modulators of immune response.

A nuclear and/or cytoplasmic GSTP1 immunostaining occurs – at variable intensity – in most cell types.

Images describing the GSTP1 staining pattern in normal tissues obtained by the antibody MSVA-685R are shown in our “Normal Tissue Gallery”.

The ubiquitous staining of GSTP1 across all tissue types is largely consistent with the RNA data described in the Human Protein Atlas (Tissue expression GSTP1). 

Positive control = Prostate: A strong nuclear and cytoplasmic GSTP1 staining should be seen in all basal cells of the prostate.

Negative control = GSTP1 staining must be absent in Sertoli cells and in maturing germ cells (weak positivity should be seen in spermatogonia).

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-685R at a dilution of 1:150 at 37°C for 60 minutes. Visualization of bound antibody by the EnVision Kit (Dako, Agilent) according to the manufacturer’s directions.

• The diagnostic utility of GSTP1 IHC for cancer and preneoplastic disease needs to be investigated.
• The prognostic relevance of GSTP1 expression in tumors should be explored further. 
• The predictive role of increased and/or reduced or absent GSTP1 expression for cancer treatments needs to be evaluated.
• The interaction of GSTP1 with other cellular pathways needs to be better understood.

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 GSTP, orthogonal validation is not well suited due to the ubiquitous expression of the protein. Ubiquitous GSTP1 protein expression seen by the antibody MSVA-685R is consistent, however, 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 GSTP1). Also in line with the summarized RNA data, GSTP1 immunostaining by MSVA-685R was largely absent in the testis and in the liver. These two organs exhibit – by far – the lowest levels of GSTP1 RNA expression (close to zero).

Comparison of antibodies: True GSTP1 protein expression in all cell types found by MSVA-685R is corroborated by identical stainings obtained by another commercially available independent antibody (termed “validation antibody”). The similarity of staining also includes the same variability of staining patterns between different cell types in individual tissues such as  variations between different renal tubuli, different layers of squamous epithelium, and surface versus crypt differences in the intestinal epithelium staining. Additional cytoplasmic stainings seen in skeletal muscle and in maturing germ cells of the testis which were only observed by the validation antibody but not by MSVA-685R were considered cross-reactivities of the validation antibody.

Normal tissue gallery