Andrew B. Nixon, PhD, ​MBA, director, Phase 1 Biomarker Laboratory, associate professor of medicine, Duke University School of Medicine, discusses the role of immunohistochemistry (ICH) and multiplex polymerase chain reactions (PCRs) tests in detecting microsatellite instability–high (MSI​-H) tumors.

Historically, IHC has been the gold standard to measure MSI ​status in patients with cancer, says Nixon. 

Notably, this technique is practical and readily available in many laboratories.

Moreover, IHC detect​s the 4 genes that regulate the mismatch repair mechanism: MLH1, MSH2, MSH6, and PMS2​, Nixon explains. When one of these genes are lacking, the tumor is deemed MSI-H.  

​Multiplex PCR, which look​s for differences in tandem repeats found at the end of each chromosome​, could be considered a second gold standard in identifying MSI status, Nixon says. When differences ​are found ​in multiplex PCR testing, the tumor is understood to be MSI-H.

Although IHC and multiplex PCR have ​historically been the 2 main techniques that have been utilized, next-generation sequencing may play a role in the future ​of MSI testing as more patients are molecularly profiled, Nixon concludes.

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Andrew B. Nixon, PhD, ​MBA, discusses the role of immunohistochemistry and multiplex polymerase chain reactions tests in detecting microsatellite instability–high tumors.

Dr. Nixon on the Role of IHC and Multiplex PCR in Detecting MSI-H Tumors 

Andrew B. Nixon, PhD, ​MBA, director, Phase 1 Biomarker Laboratory, associate professor of medicine, Duke University School of Medicine, discusses the role of microsatellite instability (MSI) in cancer.

MSI describes an accumulation of mutations in the telomere region of the chromosome, says Nixon. These mutations represent insertions or deletions, also known as tandem repeats.

Tandem repeats are measurable and occur in ​the DNA when nucleotide pattern repetitions are near one another​, Nixon says.

Notably, a large number of mutations or alterations is in this region of the chromosome, the tumor is deemed microsatellite ​instable, ​says Nixon. This instability is due to a functional loss of DNA mismatch repair (MMR) enzymes.

Although these consist of many proteins, ​MLH1, MSH2, MSH6, and PMS2 are looked at most closely. ​Moreover, an alteration in these MMR proteins results in an MSI phenotype, Nixon concludes. 

Andrew B. Nixon, PhD, ​MBA, discusses the role of microsatellite instability in cancer.

Andrew B. Nixon, PhD, MBA

Articles

Dr. Nixon on the Role of IHC and Multiplex PCR in Detecting MSI-H Tumors

Dr. Nixon on the Role of MSI in Cancer