MSH6 [BC19]

Product Description

MSH6 is a heterodimer of MSH2 and binds to DNA containing G/T mismatches. The MSH2-MSH6 complex recognizes a single-based mispair insertion/deletion loop. An alteration of microsatellite repeats is the result of slippage owing to strand misalignment during DNA replication and is referred to as microsatellite instability (MSI).^1,2 These defects in DNA repair pathways have been related to human carcinogenesis. Studies have shown the mutations in MSH-1, MSH2, MSH6, and PMS2 genes contribute to the development of sporadic colorectal carcinoma. The repair of mismatch DNA is essential to maintaining the integrity of genetic information over time.^1,2 Recently, a heterogeneous pattern of MSH6 expression was described in rare cases of colorectal, endometrial and sebaceous tumors.² In this pattern, areas of strong MSH6 expression are juxtaposed with areas of complete loss of expression. Patients with colorectal carcinoma that is mismatch-repair-deficient and confirmed with immunohistochemistry (IHC) (MSH2/MSH6 negative or MLH1/PMS2 deleted) have shown objective response to PD-1 antibody, pembrolizumab.³ PD-L1 IHC test has been demonstrated to be a useful predictive marker for anti-PD-1 immunotherapy in colorectal carcinoma.⁴

Specifications

1. Renkonen E, et al. Altered expression of MLH1, MSH2, and MSH6 in predisposition to hereditary nonpolyposis colorectal cancer. J Clin Oncol. 2003; 21:3629-37.
2. Graham RP, et al. Heterogenous MSH6 loss is a result of microsatellite instability within MSH6 and occurs in sporadic and hereditary colorectal and endometrial carcinomas. Am J Surg Pathol. 2015; 39:1370-6.
3. Lee LH, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol. 2016; 29:1333-42.
4. Le DI, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509-20.
5. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
6. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.