MSH2 (MSVA-902M)

Recombinant Mouse monoclonal / IgG 1:100 – 1:200 Research Use Only Nuclear Human MSVA-902M BAT26; COCA1; DNA mismatch repair protein Msh2; FCC1; hMSH2; HNPCC1; LCFS2; MSH2; MutS homolog 2; MutS homolog 2 colon cancer nonpolyposis type 1; MutS protein homolog 2 Tonsil: Virtually all mantle zone B-cells must show an at least weak to moderate nuclear staining. A moderate to strong nuclear staining must be seen in the germinal centre B-cells. Colon adenocarcinoma with previously documented loss of MSH2 expression: no nuclear staining should be seen in cancer cells, while a nuclear staining must be seen in stromal and inflammatory cells. MSH2 is a pivotal protein for DNA mismatch repair. MSH2 is a 104,7 kDa protein coded by the MSH2 gene at 2p21-p16.3. The MSH2 protein belongs to the Mutator S (MutS) family of proteins that play a key role in DNA damage repair. DNA mismatches commonly occur as a result of DNA replication errors, genetic recombination, or other chemical and physical factors. Recognizing those mismatches and repairing them is extremely important for cells and a failure to do so results in microsatellite instability. MSH2 combines with either MSH6 to form the repair complex MutS alpha or MSH3 to form the DNA repair complex MutS beta. MSH2/MSH6 or MSH2/MSH3 dimerization occurs in the cytoplasm before the dimers are imported into the nucleus. MutS alpha and MutS beta recognize mispaired bases in the DNA and bind to it. In a process involving the exchange of ADP for ATP and a conformational change of MutS alpha/beta, downstream events are then triggered that lead to the repair of the damaged DNA. MSH2 is  the second most commonly mutated gene (38%) in heredi... A nuclear MSH2 immunostaining is seen in virtually all cells. The highest levels of MSH2 expression are seen in lymphocytes of the cortex of the thymus. In gastrointestinal tract, surface epithelial cells and stomach glands show the lowest staining levels. MSH2 immunostaining is weak to moderate in the brain. These findings are largely comparable to the RNA and protein data described in the Human Protein Atlas (Tissue expression MSH2) Suggested positive tissue control : Tonsil: Virtually all mantle zone B-cells must show an at least weak to moderate nuclear staining. A moderate to strong nuclear staining must be seen in the germinal centre B-cells. Suggested negative tissue control: Colon adenocarcinoma with previously documented loss of MSH2 expression: no nuclear staining should be seen in cancer cells, while a nuclear staining must be seen in stromal and inflammatory cells. In the colon epithelium, the MSH2 staining intensity decreases from the bottom to the top of the crypts. Pitui... Most tumors show a MSH2 expression of variable intensity. A loss of MSH2 indicating a mismatch repair deficiency can occur in many different tumor types. A loss of MSH2 often occurs in combination with a loss of MSH6. Colorectal adenocarcinoma, gastric adenocarcinoma, and endometroid carcinomas of the uterus and the ovary show the highest rates of mismatch repair deficiency (5-15%). Mismatch repair deficiency can also occur in virtually all other tumor entities, typically at a frequency of 0,5-2%. The TCGA findings on MSH2 RNA expression in different tumor categories have been summarized in the Human Protein Atlas. Colorectal adenocarcinoma with strong MSH2 immunostaining in cancer cells and in stromal cells Colorectal adenocarcinoma with strong MSH2 immunostaining in stromal and inflammatory cells but lack of MSH2 staining in cancer cells Adenocarcinoma of the ampulla Vaterii showing a strong MSH2 immunostaining in cancer cells and in stromal cells 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 ... The clinical relevance of MSH2 expression levels in cancer is not clear. Particularly high levels of MSH2 have been suggested to be linked with poor prognosis in certain cancers. 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: The staining pattern the antibody MSVA-902M is consistent with the RNA expression data derived from 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 MSH2) . However, since virtually all tissues were found positive by both methods, this concordance of data per se not very ascertaining. Comparison of antibodies: The patterns ...