Abstract 4221: Development and evaluation of cell line-derived FFPE reference material for MSI assay validation

Microsatellite Instability (MSI) is defined by variance in the repeat count of microsatellite motifs and occurs in cells that are deficient in one or more mismatch repair proteins. MSI is present in varying cancer types, but is most commonly found in colorectal, gastric and endometrial cancer. Patients with early stage colorectal cancers that display MSI have a better prognosis and show a better response to chemotherapy compared to those with microsatellite stable tumors. MSI alongside additional markers such as tumor mutational burden is also a positive predictive biomarker for immune checkpoint inhibition Identification of MSI tumors in the diagnostic laboratory is traditionally performed by fluorescent multiplex PCR, evaluating the microsatellite length of two mononucleotide repeats and three dinucleotide repeats (recommended NCI Panel) or a commercially available kit, consisting of five mononucleotide markers alongside IHC staining for the four MMR proteins MSH2, MSH6, MLH1, and PMS2. With the increase in MSI testing related to the recent FDA approval of Keytruda ® , several companies and laboratories are now developing newer and better PCR-based and next-generation sequencing assays to assess MSI. To control for error, we have developed a pair of cell line-derived MSI/MSS reference samples covering the most commonly used MSI biomarkers. MSI/MSS cell lines were mixed at biologically-relevant ratios and processed into FFPE to serve as a whole-process control. Our data support the suitability of this material on a variety of different platforms and with a high degree of consistency throughout various FFPE batches. In conclusion, our cell line-derived reference samples represent a commutable control to support MSI assay development and validation. Citation Format: Takahiro Matsusaka, Eva-Maria Surmann, Sian Constantine, Hannah Child, Julie Wickenden. Development and evaluation of cell line-derived FFPE reference material for MSI assay validation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4221.