Mismatch Repair (MMR) Protein Panel Test Cost & Procedure

The identification and rectification of occasional genetic mutations that take place during DNA replication depend on DNA mismatch repair (MMR) proteins. Neoplasia formation is more likely when MMR function is impaired (dMMR). Finding dMMR in tumours may indicate a high possibility of the inherited cancer disorder Lynch syndrome and may indicate a poor clinical response to several conventional chemotherapies, but may also indicate a higher likelihood of response to immunotherapy. This review offers a current update on the biology of MMR proteins, the genes that encode them, and the processes that lead to the emergence of dMMR. A review of the detection and importance of dMMR in ordinary clinical practise is then included.

Used for

Identifying patients at risk for hereditary nonpolyposis colon cancer/Lynch syndrome by tumour tissue analysis

Claims information

Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC), is an inherited cancer syndrome with an autosomal dominant pattern that increases the risk of developing colorectal, endometrial, gastric, upper urinary tract, and other cancers. A germline mutation in one of the many genes involved in DNA mismatch repair is present in people with HNPCC/Lynch syndrome. The bulk of mutations linked to HNPCC/Lynch syndrome are found in MLH1 and MSH2, although there are also known variants in MSH6 and PMS2.

Several methods can be used to assess people whose personal or family history of cancer is suggestive of HNPCC/Lynch syndrome. The initial step is typically to examine tumours for the traits shared by those who have HNPCC/Lynch syndrome, which include microsatellite instability (presence of numerous alterations in a class of repetitive DNA called microsatellites) and loss of protein expression of 1 or more of the genes connected to HNPCC/Lynch syndrome.

Importance 

Up to 15% of sporadic colorectal cancers (CRCs) have a DNA mismatch repair (MMR) defect, which is a hallmark of Lynch syndrome, which is more common in young adults (age, 50 years) with CRC. The prognosis and responsiveness to systemic therapy are affected by mismatch repair failure, which can be brought on by germline mutations or epigenetic inactivation. Unrepaired repetitive DNA sequences occur, which raises the likelihood of developing many malignant tumours.

Objective

Analyzing nonadherence to long-standing testing guidelines in younger persons and evaluating the use of MMR deficient testing in adults with CRC using a recent national data set to uncover potential risk variables for nonadherence to me

Cautions

It is impossible to distinguish between somatic and germline mutations when one or more of the MMR genes tested show missing protein expression.

Genetic counselling should be offered prior to immunohistochemistry (IHC) testing because the results could suggest the potential of a germline mutation.

The clinical findings, family history, and other laboratory data should be considered when interpreting test results. If the data provided to us is incorrect or lacking, we may interpret the results incorrectly.