MODAPLEX MSI Analysis Kit

Features

• Simultaneous detection of 7 markers for dMMR status assessment
• Fast results – 4 h from DNA to result
• Evaluate results within minutes with the intuitive MODAPLEX Reporter software
• Evaluate microsatellite instability by visual comparison of allelic peak shapes from tumor and adjacent native tissue
• Tested with colorectal and endometrial cancer samples

The MODAPLEX MSI Analysis Kit is a qualitative and comprehensive polymerase chain reaction (PCR)-based multiplex assay for the detection of microsatellite instability in human DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue on the MODAPLEX instrument.

Biomarkers

Mononucleotide marker: Bat-25, Bat-26, NR-21, NR-24, Mono27

Dinucleotide marker: D5S346, D17S250

Internal controls: HLD131, HLD133

Scientific Background

Microsatellite instability (MSI) occurs when the DNA mismatch repair is defective (dMMR) resulting in frameshifts in the repeat sequences of the microsatellites which can be detected.  The presence of MSI is associated with a high mutational burden due to mutational rates of 10-100 mut/Mb (hypermutation) [1]. The marker, initially clinically implemented through the Bethesda Guidelines (1998, 2002) for the identification of patients with Lynch Syndrome, became even more relevant as a positive prognostic marker for patients with colorectal and endometrial cancer [2, 3, 4, 5].

Additionally, tumors with defective MMR show a strong response to immune-checkpoint inhibitors and consequently immune checkpoint therapies have been approved both by the FDA and EMA for a range of cancer entities that have been characterized as MSI high [6,7].

When the Cancer Genome Atlas Research Network (TCGA) performed an integrated genomic, transcriptomic, and proteomic characterization of endometrial carcinoma, MSI was identified as a biomarker one of the four subgroups [5]. This molecular classification has now been incorporated into endometrial carcinoma guidelines, published by the European Society of Gynaecological Oncology (ESGO), the European Society of Pathology (ESP) and the European Society for Medical Oncology (ESMO) [8,9].

1. Li, K. et al. Microsatellite instability. A review of what the oncologist should know. Cancer Cell Int 20, 16; 10.1186/s12935-019-1091-8 (2020).
2. Boland, C. R. et al. A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: Development of International Criteria for the Determination of Microsatellite Instability in Colorectal Cancer. Cancer Res, 5248–5257 (1998).
3. Umar, A. et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. Journal of the National Cancer Institute 96, 261–268; 10.1093/jnci/djh034 (2004).
4. Koncina, E. et al. Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer. Updates and Challenges. Cancers 12; 10.3390/cancers12020319 (2020).
5. Kandoth, C. et al. Integrated genomic characterization of endometrial carcinoma. Nature 497, 67–73; 10.1038/nature12113 (2013).
6. Luchini, C. et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden. A systematic review-based approach. Ann Oncol 30, 1232–1243; 10.1093/annonc/mdz116 (2019).
7. Eso, Y. et al. Microsatellite instability and immune checkpoint inhibitors. Toward precision medicine against gastrointestinal and hepatobiliary cancers. J Gastrointest Oncol 55, 15–26; 10.1007/s00535-019-01620-7 (2020).
8. Concin, N. et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 31, 12–39; 10.1136/ijgc-2020-002230 (2021).
9. Oaknin, A. et al. Endometrial cancer. ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 33, 860–877; 10.1016/j.annonc.2022.05.009 (2022).