MSI analysis in patients with GIST with lynch syndrome.

Abstract

e23510 Background: Lynch Syndrome due to mutations in one of DNA mismatch repair (MMR) genes, is found in patients with colon cancer (3%).The mutations in these DNA repair genes induce genetic instability and development of ovarian, endometrial, urothelial, gastrointestinal and biliary tract carcinoma. Methods: In our center, 31 patients with Lynch syndrome are followed in Oncology Department in multidisciplinary team according to regional diagnostic therapeutic assistance paths and international guidelines. Immunohistochemical staining (IC) for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) and microsatellite instability testing (MSI) by PCR real time easyPGX were performed in colon cancer, genetic testing has been preceded by genetic counseling. When GIST diagnosis occurred in patients with colon cancers and Lynch syndrome, IC and MSI were performed in GIST too. Results: MSI-H has been detected in synchronous colo-rectal cancer in 2 patients with GIST. Pathogenetic germline mutations in MSH2 gene were observed in both patients. In 1 female patient with gist of duodenum (very low risk according to Miettinen classification) with previous endometrial cancer and sincronous PT3N0 rectal cancer, we observed MSI-stable in IC and PCR, KIT/PDGFRα wild type in Next GenSequencing analysis, BRAF wild type (PCR-real time), SDH-B + (IC), NTRK 1 (exon 9-10, exon 1-12 del, exon 12), NTRK 2 (exon 12-15.exon 16-17), exon 14, NTRK 3 (exon 14, exon 15) no gene fusion by PCR-real time (CE.IVD kit easy NTRK). In 1 male patient with ileal GIST (intermediate risk according to Miettinen classification ) with ileal adenocarcinoma pT3N0, we observed KIT exon 11 mutated, MSI-stable in IC, when we repeated the analysis using PCR real time EasyPGX, we observed high instability of microsatellites. Conclusions: For the first time we observed in Lynch Syndrome MSH2 mutated, simolutaneous GIST and colon cancer in the same site of ileum and PCR analisys detected a rare exemple of microsatellite instability in GIST.