Extracolonic tumours in a pedigree with EPCAM-related Lynch Syndrome

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Extracolonic tumours in a pedigree with EPCAM-related Lynch Syndrome

Monday, 26.09.2022


Joana Alves da Silva1, Sérgio Castedo2,3,4,5, Isabel Pedroto1,3, Ricardo Marcos-Pinto1,3

1 Serviço de Gastrenterologia do Centro Hospitalar Universitário do Porto

2 Institute of Molecular Pathology and Immunology, University of Porto

3 Instituto de Investigação e Inovação em Saúde da Universidade do Porto (i3S)

4 Serviço de Genética Médica, Centro Hospitalar Universitário de São João

5 Faculdade de Medicina da Universidade do Porto

6 Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto

 

Abstract:

Lynch Syndrome is characterized by phenotypic and genotypic heterogeneity. Despite scarce evidence, individuals with an EPCAM deletion appear to have a comparable risk of colorectal cancer (CRC) as MSH2 mutation carriers, but a lower risk of extracolonic cancer (such as endometrial cancer) unless the deletion extends close to the promoter of MSH2. A genotype-phenotype correlation is yet to be established for EPCAM alterations. In this report, we describe a family with EPCAM deletion characterized by a particularly aggressive phenotype and extracolonic cancer. We present a family with 5 members carrying an EPCAM deletion encompassing exons 8 and 9. Three female family members presented CRC at the ages of 32, 44 and 60 (mucinous moderately and well-differentiated adenocarcinoma); in two of them metachronous colon cancers and advanced adenomas were diagnosed in the intensive surveillance program. Two female patients (42 and 63 years-old) presented with gastric cancer (GC). Two patients presented with small bowel cancer at 51 and 60 years-old - the first one presented a metachronous jejunal cancer at 68 years. Only one family member was submitted to hemithyroidectomy due a right-lobe Hürthle cell carcinoma at 56 years-old. This report illustrates the existence of intrafamilial clinical heterogeneity among carriers of this EPCAM alteration, and hence the difficulty in predicting phenotype for EPCAM-associated Lynch syndrome.


European Journal of Medical Genetics

https://pubmed.ncbi.nlm.nih.gov/35367635/