107P Unveiling mismatch repair deficiency (dMMR) and microsatellite-instability high (MSI-H) detection in cancer patients (pt) using a next-generation sequencing (NGS)-based molecular pre-screening program (MPP)

• DOI: 10.1016/j.esmoop.2023.101917
• Publication Date: 2023-10-06T10:09:25Z
• Authors: L. Notario Rincon; M.A. Bergamino; M. Ochoa de Olza ...; E. Carcereny; A. Urbizu; A.M. Muñoz-Mármol; L. Arnaldo; D. Azuara; A. Alay Badosa; X. Matias-Guiu; M. Jimeno; A. Hernandez; D. Balaña; C. Fina Planas; M. Gil Martín; J.J. Soto Castillo; J. Martin-Liberal; C. Lazaro; C. Sanz; C. Hierro
• Keywords: Microsatellite Instability; MSH2; MLH1

The highest prevalence of MSI is observed in colorectal (CRC), endometrial, and gastric cancers. Lately, has expanded its clinical utility as predictive biomarker to immunotherapy (IO). IHC and/or PCR are the gold standard methods for detection, though NGS arises a promising approach expand spectrum malignancies which we can detect dMMR or MSI-H. We performed multicentric retrospective study adult pt with advanced solid evaluated through coordinated MPP at three different Catalan Institute Oncology centres Catalonia, Spain. Tumors were profiled Oncomine Comprehensive Assay v3 (OCAv3) Illumina TruSight 500 (TSO500) assay. Both tests detected mutations (mut) MMR genes, but TSO500 also included MSI-H percentage repeats. Molecular results weekly reviewed dedicated molecular tumor boards (MTB) correlated IHC/PCR. aim was describe characteristics dMMR/MSI-H their benefit (ClinBen) if treated IO, defined response stable disease >4 months. From Mar'21 Jul'23, 1514 analysed 23 cases considered dMMR/MSI-H. Histologies CRC (12), NSCLC (6), endometrial (1) breast (1), carcinoma unknown origin (CUD; 1), adrenal (AC; 1) glioma (1). Mut genes 19 tumors (14/808 OCAv3 5/706 TSO500): MLH1mut (9), MSH6mut (5), MSH2mut (5) PMS2mut (2). Two harbored co-existing MSH2/MSH6mut. Before results, only 10 MMR-mutated previously identified by IHC/PCR all them had high (9 CRC, 1 endometrial). Lynch sd. established 6 these cases. Noteworthy, 9 whom 4 no underlying MMRmut. ClinBen achieved out IO. Our show that MTB help molecularly characterize multiple types, widening detection dMMR/MSI Uncommon histologies, such CUD, AC gliomas, therapeutically from this approach.