Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability.
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.
Svrcek
Magali
M
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service d'Anatomie Pathologique, Paris, France. magali.svrcek@sat.aphp.fr
El-Bchiri
Jamila
J
Chalastanis
Alexandra
A
Capel
Emilie
E
Dumont
Sylvie
S
Buhard
Olivier
O
Oliveira
Carla
C
Seruca
Raquel
R
Bossard
Céline
C
Mosnier
Jean-François
JF
Berger
Françoise
F
Leteurtre
Emmanuelle
E
Lavergne-Slove
Anne
A
Chenard
Marie-Pierre
MP
Hamelin
Richard
R
Cosnes
Jacques
J
Beaugerie
Laurent
L
Tiret
Emmanuel
E
Duval
Alex
A
Fléjou
Jean-François
JF
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