Gastric cancer in Lynch syndrome is associated with underlying immune gastritis

Adar, Tomer; Friedman, Madeline; Rodgers, Linda; Shannon, Kristen M.; Zukerberg, Lawrence; Chung, Daniel C.

doi:10.1136/jmedgenet-2018-105757

Cited by 22 publications

(26 citation statements)

References 5 publications

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“…LS-associated ovarian cancers are typically of endometrioid or clear cell type, with some tumour-infiltrating lymphocytes [79,80,85,86]. LSassociated gastric carcinomas are mostly of the intestinal-type with fewer diffuse-type, and rarely of mucinous type, and an associated immune gastritis is reported [87][88][89][90]. LS-associated small intestinal adenocarcinomas often display mucinous, signet-ring cell, or medullary differentiation, with tumour-infiltrating lymphocytes and Crohn-like reactions, as do ampullary adenocarcinomas [91].…”

Section: Pathology Of Lynch Syndrome Cancersmentioning

confidence: 99%

Molecular pathology of Lynch syndrome

Cerretelli

Ager

Arends

et al. 2020

The Journal of Pathology

124

106

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Lynch syndrome (LS) is characterised by predisposition to colorectal, endometrial, and other cancers and is caused by inherited pathogenic variants affecting the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. It is probably the most common predisposition to cancer, having an estimated prevalence of between 1/100 and 1/180. Resources such as the International Society for Gastrointestinal Hereditary Cancer's MMR gene variant database, the Prospective Lynch Syndrome Database (PLSD), and the Colon Cancer Family Register (CCFR), as well as pathological and immunological studies, are enabling advances in the understanding of LS. These include defined criteria by which to interpret gene variants, the function of MMR in the normal control of apoptosis, definition of the risks of the various cancers, and the mechanisms and pathways by which the colorectal and endometrial tumours develop, including the critical role of the immune system. Colorectal cancers in LS can develop along three pathways, including flat intramucosal lesions, which depend on the underlying affected MMR gene. This gives insights into the limitations of colonoscopic surveillance and highlights the need for other forms of anti-cancer prophylaxis in LS. Finally, it shows that the processes of autoimmunisation and immunoediting fundamentally constrain the development of tumours in LS and explain the efficacy of immune checkpoint blockade therapy in MMR-deficient tumours.

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Section: Pathology Of Lynch Syndrome Cancersmentioning

confidence: 99%

Molecular pathology of Lynch syndrome

Cerretelli

Ager

Arends

et al. 2020

The Journal of Pathology

124

106

View full text Add to dashboard Cite

show abstract

“…In LS, the majority of gastric cancers are of the intestinal type, showing high microsatellite instability and loss of MMR protein expression. 14,18,19 Only 20% of LS-associated gastric cancers were reported to be H pylori positive in a Finnish study, and H pylori infection rates in LS carriers with or without first-degree relative with gastric cancer were equivalent according to a study from the Netherlands, suggesting that segregation of H pylori infection within a family is perhaps not the etiology of this familial risk. 18,20 None of the gastric cancers in the small case series were associated with H pylori.…”

mentioning

confidence: 96%

“…18,20 None of the gastric cancers in the small case series were associated with H pylori. 14 Knowledge of LS-specific cancer incidence and risk factors helps define high-risk patients and tailor surveillance accordingly. We know from the Prospective Lynch Syndrome Database (PLSD) that LS survival rates after gastric cancer diagnosis approached 61% at 5 years.…”

mentioning

confidence: 99%

Refining Risk Factors for Gastric Cancer in Patients With Lynch Syndrome to Optimize Surveillance Esophagogastroduodenoscopy

Mankaney

Macaron

Burke

2020

Clinical Gastroenterology and Hepatology

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“…However, due to the lack of effective evaluation and prediction methods for most patients after surgery, the local recurrence rate and metastasis rate are high, leading to poor prognosis of patients. Somatic mutations in GC are caused by relatively many factors, including DNA repair defects, inherent errors in DNA replication mechanism, DNA enzyme modification, and exogenous exposure [14].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer

Wang

et al. 2021

Journal of Oncology

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Background. The purpose of this study was to investigate the change of tumor mutation burden (TMB) in gastric cancer (GC) and its relationship with prognosis. Methods. A total of 262 patients with GC from January 2018 to December 2019 were included in this study. All patients were in the advanced stage and were treated with surgical removal of D2 lymph nodes and dissection. Clinical data and gene expression profile data of the GC dataset in The Cancer Genome Atlas were collected. Patients were randomly divided into a high-level group and a low-level group according to the TMB of 8 mutations/Mb. TMB of GC was calculated based on cell mutation data. Cox regression model was used to evaluate the relationship between TMB and prognosis of GC patients. Results. The total mutation rate of 262GC patients was 92.85%. The top 5 mutant genes were TP53, RB1, ARID1A, KMT2B, and RET. The expression level of TMB in GC patients was statistically significant with age, drinking history, and differentiation type. 94 of the 262 patients died, and 168 survived during the follow-up period. Patients with a high level of TMB had a worse prognosis than those with low level of TMB. The results of univariate and multivariate logistic analysis showed that the overall survival rate of GC patients was statistically significant with age, drinking history, clinical stage, differentiation type, and TMB. Conclusion. GC patients are often accompanied by changes in TMB, and its expression level is closely related to the degree of pathological differentiation, which is an independent factor affecting the prognosis of GC patients. High TMB value can evaluate the prognosis and provide a reference for the formulation of clinical treatment plans for GC patients.

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Gastric cancer in Lynch syndrome is associated with underlying immune gastritis

Cited by 22 publications

References 5 publications

Molecular pathology of Lynch syndrome

Molecular pathology of Lynch syndrome

Refining Risk Factors for Gastric Cancer in Patients With Lynch Syndrome to Optimize Surveillance Esophagogastroduodenoscopy

Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer

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