title: Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability.
abstract: OBJECTIVE
  Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency has been reported to occur at variable frequencies in inflammatory bowel disease-associated intestinal neoplasias (IBD-Ns). We investigated a large series of IBD-N for associations between MSI and several biologic and clinical parameters related to tumors, patients, and their treatment.
  
  
  METHODS
  A total of 277 IBD-Ns in 205 patients were screened for MSI. Biologic and clinical variables of patients with high levels of DNA microsatellite instability high (MSI-H) were collected and compared with those associated with 33 MSI-H non-IBD colorectal cancers (CRCs).
  
  
  RESULTS
  A total of 27 IBD-Ns from 17 patients were found to be MSI-H. Compared with sporadic MSI-H CRCs, patients presented with a younger age at diagnosis, and there was no female predominance and no right-sided predominance. Unlike sporadic MSI-H CRCs, MSI-H IBD-Ns presented with heterogeneous mismatch repair defects involving MLH1, MSH2, MSH6, or PMS2, and a low frequency of MLH1 promoter methylation. They exhibited frequent BRAF mutations and frameshift mutations in genes containing coding repeat sequences.
  
  
  CONCLUSIONS
  The mechanisms underlying MMR deficiency in MSI-H IBD-Ns are different from those in sporadic MSI-H tumors and seem to be more related to those observed in hereditary MSI-H tumors. However, BRAF mutations were observed in MSI-H IBD-Ns, similar to sporadic MSI-H tumors, but unlike hereditary MSI-H tumors. Finally, the mutational events in target genes for instability are the same in MSI-H IBD-N tumors as in non-IBD sporadic and hereditary colorectal MSI-H cancers, indicating a colon-related repertoire of target gene alterations.
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service d'Anatomie Pathologique, Paris, France. magali.svrcek@sat.aphp.fr
authors: Magali
authors: M
authors: Svrcek
authors: Jamila
authors: J
authors: El-Bchiri
authors: Alexandra
authors: A
authors: Chalastanis
authors: Emilie
authors: E
authors: Capel
authors: Sylvie
authors: S
authors: Dumont
authors: Olivier
authors: O
authors: Buhard
authors: Carla
authors: C
authors: Oliveira
authors: Raquel
authors: R
authors: Seruca
authors: Céline
authors: C
authors: Bossard
authors: Jean-François
authors: JF
authors: Mosnier
authors: Françoise
authors: F
authors: Berger
authors: Emmanuelle
authors: E
authors: Leteurtre
authors: Anne
authors: A
authors: Lavergne-Slove
authors: Marie-Pierre
authors: MP
authors: Chenard
authors: Richard
authors: R
authors: Hamelin
authors: Jacques
authors: J
authors: Cosnes
authors: Laurent
authors: L
authors: Beaugerie
authors: Emmanuel
authors: E
authors: Tiret
authors: Alex
authors: A
authors: Duval
authors: Jean-François
authors: JF
authors: Fléjou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged