Clinical Implications

Microsatellite instability (MSI) results from the systematic accumulation of deletions/insertions in short repetitive DNA sequences in tumor cells with a deficient mismatch repair (MMR) system. MSI occurs in approximately 15% of all colorectal cancers and is clinically useful to identify patients with hereditary nonpolyposis colorectal cancer (HNPCC, Lynch Syndrome) caused by germline mutations of MMR genes. MSI status may also predict cancer response/resistance to certain chemotherapies.

To standardize MSI analysis, a 1997 National Cancer Institute (NCI) workshop recommended a reference panel of five microsatellite markers for the detection of MSI and established MSI classification guidelines based on the results. The reference panel, referred to as the Bethesda panel, consists of two mononucleotide loci (Big Adenine Tract or BAT-25 and BAT-26) and three dinucleotide loci (D2S123, D5S346 and D17S250). Using the Bethesda panel, cancers with instability at 2 or more of these loci were interpreted as MSI-high (MSI-H), and cancers with no instability at any of the five loci were considered Microsatellite Stable (MSS). The OncoMate™ MSI Dx Analysis System generates allelic profiles from tumor and non-tumor FFPE tissue samples from the same patient through polymerase chain reaction (PCR) amplification of DNA microsatellite markers, followed by size separation of the amplified markers using capillary electrophoresis. MSI status is determined by comparing the allelic profiles. An expansion or reduction in the length of repetitive DNA sequences in the tumor cell DNA when compared to the normal cell DNA from the same patient indicates MSI. Normal and tumor tissue from the same patient must be tested at the same time and data from both samples must be available for comparison for results to be valid.

Specimen Requirements

Acceptable specimens for the assay are formalin-fixed, paraffin-embedded tissue specimens with a fixation time of 6-48 hours.

Volume

One representative paraffin block is preferred. Alternatively, for resection specimens a minimum of 5 unstained tissue sections (5 µm thick) is required.

Storage and Shipment Instructions

Maintain and ship specimens at ambient temperature.

Limitations

Insufficient tumor content may not allow the detection of MSI instability: 10% of tumor cells is required. Tumor content is evaluated prior to analysis and macrodissection is performed. Fixatives other than formalin or prolonged fixation time may give rise to inadequate results.

The OncoMate™ MSI Dx Analysis System is not intended to diagnose a specific disease. It is intended for use with patients already diagnosed with cancer who may benefit from additional genetic testing. Test results obtained using the product must be interpreted by healthcare professionals in conjunction with other clinical findings, family history and laboratory data. This product is intended for professional use only.

Turn-Around Time

Five to seven business days for respectively slides and paraffin blocks.