QF0159 Marketing Release Record

Primary Antibodies
Novocastra Mismatch Repair Protein
(MLH1)
Clone ES05 Reference Range
1 mL, 0.1 mL liquid NCL-L-MLH1 P (HIER)
7 mL BOND ready-to-use PA0610 P (HIER)
Antigen Background
MLH1, a mismatch repair protein involved in maintaining the integrity of
genetic information, alongside MSH2, MSH6 and PMS2. During DNA
replication, strand misalignment can occur resulting in alterations to
microsatellite repeats, often referred to as microsatellite instability (MSI).
These defects in DNA repair pathways have been linked to human
carcinogenesis. Mutations in the MLH1 gene have been reported to be found
in tumors with MSI, such as some forms of colon cancer eg Hereditary
nonpolyposis colon cancer (HNPCC), a subset of sporadic carcinomas and
breast cancer. Loss of expression of MLH1 has also been reported in acute
lymphoblastic leukemia, endometrial carcinoma, gastric carcinoma and
ovarian carcinoma.
Human small intestine: immunohistochemical staining for MLH1 protein using NCL-L-MLH1.
Note gradient of staining through the maturing and differentiated epithelial cells of the villi and
also in a proportion of the stromal cells. Paraffin section.
Novocastra Mismatch Repair Protein
(MSH2)
Clone 25D12 Reference Range
1 mL, 0.1 mL lyophilized NCL-MSH2 P (HIER)
7 mL BOND ready-to-use PA0048 P (HIER)
Application
Human mismatch repair protein 2 (MSH2) is involved in the initial recognition
of mismatched nucleotides during the post replication mismatch repair
process. Therefore, the loss of MSH2 function leads to the accumulation of
replication errors, which in turn may be responsible for the multiple
mutations required for multistage carcinogenesis. Mutations in mismatch
repair genes have been linked to hereditary nonpolyposis colon cancer and
to sporadic cancers which exhibit microsatellite instability. MSH2 is
reported to be expressed in the nuclei of cells from a variety of tissues
including thyroid, heart, smooth muscle and the germinal centers of
lymphoid follicles. In ileum and colon, MSH2 expression has been reported
in the crypts, the cells of which are undergoing rapid renewal. They are
responsible for the continuous production of differentiated cells which
migrate over 2 to 4 days before being sloughed into the lumen.
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Novocastra Mismatch Repair Protein
(MSH6)
Clone PU29 Reference Range
1 mL, 0.1 mL liquid NCL-L-MSH6 P (HIER)
7 mL BOND ready-to-use PA0597 P (HIER)
Antigen Background
MSH6 is a 160 kD protein which is involved in DNA mismatch repair (MMR)
and recombination pathways, when heterodimerized with MSH2. Defects in
mismatch repair systems can cause mutations and can cause DNA
microsatellite sequences to become unstable. Microsatellite instability has
been described in colorectal cancer, particularly in Hereditary Nonpolyposis
Colorectal Cancer (HNPCC) where MSH6 expression, along with other MSH
proteins, is disrupted. Immunohistochemical studies have reported that
MSH6 is strongly expressed in the nucleus of cells in normal colonic
epithelium, especially in crypts. Expression is also found in lymphocytes.
Studies have also shown that MSH6 is expressed in gastric carcinomas and
endometrial carcinomas. However, sometimes expression can be lost in
some endometrial carcinomas and colonic carcinomas with microsatellite
instability. MSH6 has been reported to be a useful marker to use in
conjunction with microsatellite instability screening to identify colon tumors
that may contain MMR gene mutations, such as HNPCC.
Product Specific Information
The use of PBS-based diluents may result in increased background staining.
Human colonic carcinoma: immunohistochemical staining for Mismatch Repair Protein 6
(MSH6) using NCL-L-MSH6. Note intense nuclear staining of a proportion of tumor cells.
Paraffin section.
Novocastra Mismatch Repair Protein
(PMS2)
Clone M0R4G
1 mL, 0.1 mL liquid NCL-L-PMS2 P (Enzyme) W
Antigen Background
Postmeiotic segregation increased 2 (PMS2), also known as PMS1 protein
homologue 2, is a DNA mismatch repair (MMR) protein. The PMS2 gene
family members are found in clusters on chromosome 7. PMS2 is a 96 kDa
mismatch repair protein closely related to MLH1, MLH3 and PMS1, which are
homologs of the bacterial mutL gene. The PMS2 protein forms a heterodimer
with the MLH1 protein which is then activated in the presence of ATP; this
complex coordinates the binding of other proteins that repair DNA errors
arising during cell preparation for cell division.
The loss of PMS2 expression in tumors can be helpful in identifying hMLH1
mutation carriers and identify their suitability for mutation analysis.
PMS2 gene defects account for a small but significant proportion of
colorectal cancers and for a substantial proportion of tumors with
microsatellite instability. PMS2 is associated with cases of the dominantly
inherited disorder Hereditary Non-Polyposis Colon Cancer (HNPCC) but more
clearly associated with a variation of HNPCC known as Turcot syndrome.
Products in this catalog are subject to regulatory approval.
Please consult your Leica Microsystems representative for availability in your region.
* For Research Use Only. Not for use in diagnostic procedures.
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