Advanced Solutions
for Advanced Pathology
MSH6 (44)
Mouse Monoclonal Antibody
Cat. No. Description
Volume
45229 IMPATH MSH6 RTU M (44)
50 Tests
44339 MSH6 RTU M (44)
7 ml Ready To Use
44698 MSH6 0,1 M (44)
100 µl liquid Concentrated
44699 MSH6 1 M (44)
1 ml liquid Concentrated
Product Specifications
Designation
IVD
Reactivity
Paraffin
Visualization
Nuclear
Control
Colon, Colon carcinoma
Stability
Up to 36 mo. at 2-8°C
Isotype
IgG
1
Manual Protocol*
• Pretreatment: Heat Induced Epitope
Retrieval (HIER)
• Primary Antibody Incubation Time:
10-30min @ 25-37°C
• 2-step polymer detection
*Please refer to product insert for complete protocol.
ImPath Protocol*
• Dewax: Dewax Solution 2 (DS2)
• Pretreatment: Retrieval Solution pH 9.0
(TR1) 32min @ 98-103°C
• Primary Antibody Incubation Time:
10-90min @ 25-37°C
• HRP 2-step Polymer (Universal) or AP
2-step Polymer (Universal) for 12 min
*Please refer to product insert for complete protocol.
Product Description
This gene encodes a protein similar to the MutS protein. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides, prior to
their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs.
The encoded protein of this gene combines with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch
that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene have been identified in individuals with
hereditary nonpolyposis colon cancer (HNPCC) and endometrial cancer. Microsatellites are repetitive DNA sequences dispersed throughout the
genome. The repetition renders them susceptible to slippage mutations. To counter this, there are families of mismatch repair (MMR) genes which
correct these errors. These repair genes include MLH1, PMS2, MSH2, and MSH6. Defective MMR genes lead to accumulation of mutations in
microsatellite regions, known as microsatellite instability (MSI). Colonic and endometrial carcinomas in HNPCC can be demonstrated to have
MSI. MSI can also be found in 17% to 23% of non-familial endometrial carcinomas: this MSI is attributable to silencing of the MLH1 gene by
promoter methylation.
HNPCC is characterized by an increased risk of colon cancer and other cancers (e.g., of the endometrium, ovary, stomach, small intestine,
hepatobiliary tract, upper urinary tract, brain, and skin). Individuals with HNPCC have an approximately 80% lifetime risk for colon cancer.
Women with HNPCC have a 20-60% lifetime risk of endometrial cancer. Among women with HNPCC who develop both colon cancer and
endometrial cancer, approximately 50% present first with endometrial cancer. 90% of patients with HNPCC have mutations of either MLH1 or
MSH2. Mutations in MSH6 have been reported in approximately 7-10% of families with HNPCC. Mutations in PMS2 account for fewer than 5%
of mutations in families with HNPCC.
MSI testing can be demonstrated by polymerase chain reaction, molecular genetic testing, and methylation analysis of tumor tissue. However,
in routine diagnostic practice, IHC is the most common clinically available method for detection of the proteins encoded by MLH1, MSH2, and
MSH6. IHC is more feasible for large scale screening programs because it is more available than MSI testing.
Microsatellite Instability
MSH6
MLH1
MSH2
PMS2
Mismatch Repair Mutations
-
+
+
+
Reference
1. Lagerstedt RK, et al. J Natl Cancer Inst. 2007 Feb 21; 99(4):291-9.
2. Niessen RC, et al. Gut. 2006 Dec; 55(12):1781-8.
3. Hansen TP, et al. Appl Immunohistochem Mol Morphol. 2006 March; 14(1):115-21.
4. Lawes DA, et al. Br J Cancer. 2005 Aug 22; 93(4):472-7.
5. Stormorken AT, et al. J Clin Oncol. 2005 Jul 20; 23(21):4705-12.
6. Rigau V, et al. Arch Pathol Lab Med. 2003; 127:694-700.
167
