Microsatellite Instability (HNPCC) Studies Test Cost & Procedure

Abstract

Immunotherapy has recently been shown to be beneficial for patients with high microsatellite instability (MSI-H)/mismatch repair deficient (dMMR) cancers, and MSI can be utilised as a genetic instability of a tumour detection indicator. However, numerous investigations have demonstrated that patients with MSI tumours exhibit a wide range of heterogeneous phenomena with regard to immunotherapy, prognosis, and chemotherapy sensitivity. Here, we primarily examine the study findings regarding MSI detection techniques, the mechanisms behind MSI development, and its associations with associated tumours.

Clinical importance

Microsatellite instability has been linked to a number of malignancies, including skin, brain, hepatobiliary tract, endometrium, ovarian, endometrial, and stomach cancers.

The most frequent occurrence of MSI is in cases of colon cancer. Worldwide, there are more than 500,000 new instances of colon cancer every year. Based on results from over 7,000 patients stratified for MSI-High (MSI-H), MSI-Low (MSI-L), or Microsatellite Stable (MSS) colon cancers, MSI-H tumours were associated with a 15% better prognosis than MSI-L or MSS tumours.

What methods are available for determining MSI status? What are these methods' benefits and drawbacks?

In order to match the resilience required when working with fragmented DNA recovered from FFPE materials, the presently Use Only MSI assay is a PCR and Capillary Electrophoresis-based test.

Since 2004, the assay has been offered and utilised on the market as a component of lab-developed tests. It is simple to use. The most effective molecular assay for identifying a DNA mismatch-repair deficit is covered by a patent and is now being used.

The MSI Assay is quick, reimbursable, and most significantly, a substantial body of research supports its utility in making judgements about colorectal cancer.

Although peer-reviewed literature shows that IHC-MMR is not a fair comparison to MSI by PCR, immunohistochemistry (IHC) examination of the presence or lack of mismatch repair proteins (MMR) is sometimes thought of as a proxy and equal analytical method.  MMR function cannot always be determined simply by the existence of MMR protein expression.

PCR and MSI

They are ideal targets for PCR amplification-based monitoring because mononucleotide repeat microsatellite sequences are particularly prone to transcription errors. In order to determine MSI, fragments from the tumour and matching normal samples are amplified using fluorescently labelled primers. The amplified fragments are separated by size using capillary electrophoresis, and further separation based on the colour of the fluorescent tag is made possible by the fluorescent labelling. Multiplexing the fluorescent markers enables the identification of several pieces of comparable size in a single reaction. MSI-high or MSI-H tumors are those with this type of microsatellite instability. Microsatellite instability can be detected by changes in size.