Clinical and pathological features in colorectal cancer associated to Lynch syndrome
Authors: O. Higuera, A. Rodriguez, N. Rodriguez-Salas, L. Ruiz-Giménez, A. Gallego, I. Ghanem, A. Custodio, D. Sanchez, L. Ostios, J. Miranda Poma, J. Feliu
Journal: Annals of Oncology (2018)

Introduction: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and accounts for approximately 3 percent of newly diagnosed cases of CRC. Lynch syndrome is an autosomal dominant disorder that is caused by a germline mutation in one of several DNA mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) or loss of expression of MSH2 due to deletion in the EPCAM gene (previously called TACSTD1). It is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. CRCs in Lynch syndrome differ from sporadic CRCs. Methods: We performed a descriptive, retrospective study of individuals and families referred to the multidisciplinary heredofamilial cancer unit (HFCU) of the Hospital Universitario La Paz between September 2008 and December 2017. We collected data on patient histories, tumor phenotypes, and results of germline DNA sequencing of patients registered in our database. The objective of the study is to describe the germline mutations in the MMR genes and to analyze the clinical and histological features of the CCRs associated with lynch syndrome. Data were analyzed using the statistical package for the social sciences 22.0 (SPSS Inc., Chicago, IL, USA). Results: We identified 75 patients from 65 different families attended by our HFCU with germline mutation in the MMR genes. 27 subjects had mutations in MSH2, being the most prevalent variant; 26 in MSH6, 20 in MLH1 and 1 in PMS2. In addition, one individual had an EPCAM deletion. Among individuals with MSH2 mutations, 3 had Muir-Torre syndrome (a variant of Lynch syndrome). 48 patients (65.7%) were referred from oncology, 20 (26.6%) from gastroenterology, 3 (4.0%) from gynecology and 4 from patient´s own request. 44% of patients have a personal history of cancer, being CRC in the 82% of cases. The median age at diagnosis of colorectal cancer was 42.3 years. At diagnosis, 4 patients had synchronous CCR whereas 6 patients who had undergone segmental resection for the first CCR developed a metachronous CRC. Regarding to the location, 47% of them arises in the right side. Concerning to the pathological features, 26% of subjects had ganglionar involvement; 31% had a brisk lymphocytic infiltrate with an intense lymphoid reaction and 36% were mucinous and poorly differentiated. At the time of the analysis, only three patients developed metastases. The 47% of patients had a personal history of malignancy related to LS, being the endometrial cancer the most frequent. In six of these with a double primary endometrial and colorectal cancer, the uterine one was diagnosed first. Conclusion: Lynch syndrome is the most common cause of inherited colorectal cancer. Germline mutation in MSH2 was the most prevalent detected in our database. Less than a half of patients had a personal history of cancer being the CRC the most frequent malignancy and it has distinct histologic features.