Advanced Solutions
for Advanced Pathology
MLH1 (G168-728)
Mouse Monoclonal Antibody
Cat. No. Description
Volume
45227 IMPATH MLH1 RTU M (G168-728)
50 Tests
44337 MLH1 RTU M (G168-728)
7 ml Ready To Use
44694 MLH1 0,1 M (G168-728)
100 µl liquid Concentrated
44695 MLH1 1 M (G168-728)
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
2a
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
MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli), also known as MLH1, is a human gene which has been identified as a locus
frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene mutL,
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, a molecular genetic test, 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
MLH1
MSH2
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; 127:694-700.
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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