491PD - Lynch-like syndrome: Characterization and comparison with EPCAM deletion carriers

Date 27 September 2014
Event ESMO 2014
Session Genetic predisposition to cancer
Topics Hereditary Syndromes
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter So Young Kang
Citation Annals of Oncology (2014) 25 (suppl_4): iv165-iv166. 10.1093/annonc/mdu332
Authors S.Y. Kang1, D.K. Chang2, K. Kim3
  • 1Department Of Pathology, Samsung Medical Center, 135710 - SEOUL/KR
  • 2Gastroenterology, samsung medical center, 135710 - seoul/KR
  • 3Pathology, samsung medical center, 135710 - seoul/KR




Colorectal cancers (CRCs) with MSI+ but without detectable germline mutation or hypermethylation in DNA mismatch repair (MMR) genes can be classified as Lynch-like Syndrome (LLS). The underlying mechanism and clinical significances of LLS are largely unknown.


We measured MSI and MMR protein expression in 4,765 consecutive CRC cases. Among these, MSI+ cases were further classified based on clinical parameters, sequencing of MMR genes or polymerase ϵ (POLE) and &dgr; (POLD1) and promoter methylation analysis of MLH1 and MSH2.


We found that MSI+ and MMR protein deficient CRCs comprised 6.3% (N = 302) of this cohort. Based on germline sequencing of 124 cases, we identified 54 LS with MMR germline mutation (LS-MMR), 15 LS with EPCAM deletions (LS-EPCAM) and 55 LLS patients. Of the 55 LLS patients, six (10.9%) had variants of unknown significance in the genes tested, and one patient had a novel somatic mutation (p.S459P) in POLE. In patients with biallelic deletions of EPCAM, all tumors and their matched normal mucosa showed promoter hypermethylation of MSH2.


We found that patients with LLS and LS-EPCAM shared clinical features that differed from LS-MMR patients, including lower frequency of fulfillment of the revised Bethesda guidelines (83.6% and 86.7% vs. 98.1% for LS-MMR) and older mean age at CRC diagnosis (52.6 and 52.7 years vs. 43.9 years for LS-MMR). The similarity between LLS and LS-EPCAM suggests LLS as a subset of familial MSI+ CRC.


All authors have declared no conflicts of interest.