Extracolonic tumours in a pedigree with EPCAM-related Lynch Syndrome.

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. Copyright © 2022. Published by Elsevier Masson SAS.

Citation

Joana Alves da Silva, Sérgio Castedo, Isabel Pedroto, Ricardo Marcos-Pinto. Extracolonic tumours in a pedigree with EPCAM-related Lynch Syndrome. European journal of medical genetics. 2022 May;65(5):104479

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PMID: 35367635

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