Abstract
Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are autosomal dominant hereditary diseases caused by germline mutations leading to the development of colorectal cancer. Moreover, these mutations result in the development of a spectrum of different tumors, including gastric cancers (GCs). Since the clinical characteristics of GCs associated with LS and FAP are not well known, we investigated clinical and molecular features of GCs occurring in patients with LS and FAP attending our Institution. The Hereditary Tumor Registry was established in 1994 at the Department of Oncologic Gastroenterology, CRO Aviano National Cancer Institute, Italy. It includes 139 patients with LS and 86 patients with FAP. Patients were recruited locally for prospective surveillance. Out of 139 LS patients, 4 developed GC—3 in the presence of helicobacter pylori infection and 1 on the background of autoimmune diseases. All GCs displayed a high microsatellite instability (MSI-H) and loss of related mismatch repair (MMR) protein. One of the FAP patients developed a flat adenoma, displaying low-grade dysplasia at the gastric body, and another poorly differentiated adenocarcinoma with signet ring cells like Krukenberg without HP infection. LS carriers displayed a risk of GC. The recognition of HP infection and autoimmune diseases would indicate those at higher risk for an endoscopic surveillance. Regarding FAP, the data suggested the need of suitable endoscopic surveillance in long survivals with diffuse fundic gland polyps.
Highlights
Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are the most frequent syndromes in hereditary colorectal cancer (CRC), causing, respectively, 6% and 1% of all CRC
LS is an autosomal dominant disorder caused by germline mutations in one of the mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2) or the EpCAM gene that mainly determines CRC
Tumor tissue of CRC and extracolonic cancers in an LS setting show two peculiar molecular features: microsatellite instability (MSI) that is characterized by length alteration within simple, repeated DNA sequences called microsatellites, and loss of MMR protein expression at immunohistochemical analyses
Summary
Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are the most frequent syndromes in hereditary colorectal cancer (CRC), causing, respectively, 6% and 1% of all CRC. Gastric adenomas are rarely observed in LS; a recent study reported PGA in 3 patients out of 15 cases of LS GC [6]. FAP is an autosomal dominant hereditary disease caused by germline mutations in the adenomatous polyposis coli (APC) gene with 80–100% penetrance, leading to the development of hundreds to thousands colorectal adenomatous polyps starting in teenage years and CRC at an average age of 39 years.
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