TY - JOUR
T1 - Prevalence of mismatch repair deficiency and Lynch syndrome in a cohort of unselected small bowel adenocarcinomas
AU - Suerink, Manon
AU - Kilinç, G. l
AU - Terlouw, Diantha
AU - Hristova, Hristina
AU - Sensuk, Lily
AU - van Egmond, Demi
AU - Farina Sarasqueta, Arantza
AU - PALGA-group collaborators
AU - Langers, Alexandra M. J.
AU - van Wezel, Tom
AU - Morreau, Hans
AU - Nielsen, Maartje
N1 - Funding Information: Funding This work was supported by a grant from the Dutch Cancer Society (KWF UL 2012-5155). Publisher Copyright: © 2021 BMJ Publishing Group. All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Aims: Previous estimates of the prevalence of mismatch repair (MMR) deficiency and Lynch syndrome in small bowel cancer have varied widely. The aim of this study was to establish the prevalence of MMR deficiency and Lynch syndrome in a large group of small bowel adenocarcinomas. Methods: To this end, a total of 400 small bowel adenocarcinomas (332 resections, 68 biopsies) were collected through the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA)). No preselection criteria, such as family history, were applied, thus avoiding (ascertainment) bias. MMR deficiency status was determined by immunohistochemical staining of MMR proteins, supplemented by MLH1 promoter hypermethylation analysis and next generation sequencing of the MMR genes. Results: MMR deficiency was observed in 22.3% of resected and 4.4% of biopsied small bowel carcinomas. Prevalence of Lynch syndrome was 6.2% in resections and 0.0% in biopsy samples. Patients with Lynch syndrome-associated small bowel cancer were significantly younger at the time of diagnosis than patients with MMR-proficient and sporadic MMR-deficient cancers (mean age of 54.6 years vs 66.6 years and 68.8 years, respectively, p<0.000). Conclusions: The prevalence of MMR deficiency and Lynch syndrome in resected small bowel adenocarcinomas is at least comparable to prevalence in colorectal cancers, a finding relevant both for treatment (immunotherapy) and family management. We recommend that all small bowel adenocarcinomas should be screened for MMR deficiency.
AB - Aims: Previous estimates of the prevalence of mismatch repair (MMR) deficiency and Lynch syndrome in small bowel cancer have varied widely. The aim of this study was to establish the prevalence of MMR deficiency and Lynch syndrome in a large group of small bowel adenocarcinomas. Methods: To this end, a total of 400 small bowel adenocarcinomas (332 resections, 68 biopsies) were collected through the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA)). No preselection criteria, such as family history, were applied, thus avoiding (ascertainment) bias. MMR deficiency status was determined by immunohistochemical staining of MMR proteins, supplemented by MLH1 promoter hypermethylation analysis and next generation sequencing of the MMR genes. Results: MMR deficiency was observed in 22.3% of resected and 4.4% of biopsied small bowel carcinomas. Prevalence of Lynch syndrome was 6.2% in resections and 0.0% in biopsy samples. Patients with Lynch syndrome-associated small bowel cancer were significantly younger at the time of diagnosis than patients with MMR-proficient and sporadic MMR-deficient cancers (mean age of 54.6 years vs 66.6 years and 68.8 years, respectively, p<0.000). Conclusions: The prevalence of MMR deficiency and Lynch syndrome in resected small bowel adenocarcinomas is at least comparable to prevalence in colorectal cancers, a finding relevant both for treatment (immunotherapy) and family management. We recommend that all small bowel adenocarcinomas should be screened for MMR deficiency.
KW - Gastrointestinal neoplasms
KW - Genetics
KW - Hereditary
KW - Intestine
KW - Neoplastic syndromes
KW - Small
UR - http://www.scopus.com/inward/record.url?scp=85094973629&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jclinpath-2020-207040
DO - https://doi.org/10.1136/jclinpath-2020-207040
M3 - Article
C2 - 33046565
SN - 0021-9746
VL - 74
SP - 724
EP - 729
JO - Journal of clinical pathology
JF - Journal of clinical pathology
IS - 11
M1 - 207040
ER -