ImPath - page 166

Antibodies for
Immunohistochemistry
MSH2 (G219-1129)
Mouse Monoclonal Antibody
Cat. No. Description
Volume
45228 IMPATH MSH2 RTU M (G219-1129)
50 Tests
44338 MSH2 RTU M (G219-1129)
7 ml Ready To Use
44696 MSH2 0,1 M (G219-1129)
100 µl liquid Concentrated
44697 MSH2 1 M (G219-1129)
1 ml liquid Concentrated
Product Specifications
Designation
IVD
Reactivity
Paraffin
Visualization
Nuclear
Control
Colon carcinoma, Colon mucosa
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
MSH2 is a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human
homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype)
found in HNPCC. 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 as it is more available than MSI testing.
Microsatellite Instability
MSH2
MLH1
MSH6
PMS2
Mismatch Repair Mutations
-
+
-
+
Reference
1. Wright CL, et al. Am J Surg Pathol. 2003; 27:1393-1406.
2. Brueckl WM, et al. Anticancer Research. 2003; 23:1773-1778.
3. Rigau V, et al. Arch Pathol Lab Med. 2003 June; 127(6):694-700.
4. Renkonen E, et al. J Clin Oncol. 2003; 21:3629-3637.
5. Hoedema R, et al. The American Surgeon. 2003 May; 69(5):387-92.
6. Christensen M, et al. Cancer 2002; 95:2422-30.
7. Wahlberg SS, et al. Cancer Research. 2002 June 15; 62:3485-3492.
8. Lanza G, et al. Modern Pathology. 2002; 15:741-749.
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