TY - JOUR
T1 - Mismatch repair deficiency in early-onset duodenal, ampullary, and pancreatic carcinomas is a strong indicator for a hereditary defect
AU - Kryklyva, Valentyna
AU - Brosens, Lodewijk A.A.
AU - Marijnissen-van Zanten, Monica A.J.
AU - Ligtenberg, Marjolijn J.L.
AU - Nagtegaal, Iris D.
N1 - Funding Information:
This study was supported by a grant from the Dutch Cancer Society (KWF Kankerbestrijding) 2016 10289.
Publisher Copyright:
© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.
PY - 2022/3
Y1 - 2022/3
N2 - Mismatch repair deficiency (dMMR) is a hallmark of Lynch syndrome (LS), but its prevalence in early-onset (diagnosed under the age of 50 years) duodenal, ampullary, and pancreatic carcinomas (DC, AC, and PC, respectively) is largely unknown. We explored the prevalence of dMMR and the underlying molecular mechanisms in a retrospectively collected cohort of 90 early-onset carcinomas of duodenal, ampullary, and pancreatic origin. dMMR was most prevalent in early-onset DCs (47.8%); more than half of those were associated with hereditary cancer syndromes (LS or constitutional mismatch repair deficiency syndrome). All dMMR AC and PC were due to LS. Concordance of dMMR with underlying hereditary condition warrants ubiquitous dMMR testing in all early-onset DC, AC, and PC.
AB - Mismatch repair deficiency (dMMR) is a hallmark of Lynch syndrome (LS), but its prevalence in early-onset (diagnosed under the age of 50 years) duodenal, ampullary, and pancreatic carcinomas (DC, AC, and PC, respectively) is largely unknown. We explored the prevalence of dMMR and the underlying molecular mechanisms in a retrospectively collected cohort of 90 early-onset carcinomas of duodenal, ampullary, and pancreatic origin. dMMR was most prevalent in early-onset DCs (47.8%); more than half of those were associated with hereditary cancer syndromes (LS or constitutional mismatch repair deficiency syndrome). All dMMR AC and PC were due to LS. Concordance of dMMR with underlying hereditary condition warrants ubiquitous dMMR testing in all early-onset DC, AC, and PC.
KW - constitutional mismatch repair deficiency syndrome
KW - early-onset ampullary carcinoma
KW - early-onset duodenal carcinoma
KW - early-onset pancreatic carcinoma
KW - germline variants
KW - Lynch syndrome
KW - microsatellite instability
KW - mismatch repair deficiency
UR - http://www.scopus.com/inward/record.url?scp=85120540206&partnerID=8YFLogxK
U2 - 10.1002/cjp2.252
DO - 10.1002/cjp2.252
M3 - Article
C2 - 34873870
SN - 2056-4538
VL - 8
SP - 181
EP - 190
JO - The journal of pathology. Clinical research
JF - The journal of pathology. Clinical research
IS - 2
ER -