Early gastric carcinomas may develop with a molecular profile differing from sporadic carcinomas occurring at a later age. In this study, we analyzed a retrospective series of 88 patients with gastric adenocarcinoma d...Early gastric carcinomas may develop with a molecular profile differing from sporadic carcinomas occurring at a later age. In this study, we analyzed a retrospective series of 88 patients with gastric adenocarcinoma diagnosed before the age of 45 years for the presence of TP53 mutations, clinicopathological features and immunohistochemistry to evaluate the expression of markers considered to be important in gastric carcinogenesis (E-cadherin, β-catenin, MUC1, MUC2, MUC5AC, MUC6 and p53). The majority of proportion of tumors were diffuse-type (70%) and advanced stage (56%). Familial history of cancer was positive in 21% of the cases. There was a significant association between altered expression of E-cadherin and β-catenin, and between p53 expression and perineural invasion. TP53 mutations were detected in 14.5% of evaluated cases, including a germline mutation (p.R337H) in a 12-year old patient. Overall survival analysis showed significant differences in relation with tumor stage and histopathology. The evaluated biomarkers did not present prognostic value in non-exploratory multivariate analyses. The low frequency of TP53 mutations in this series suggests these alterations are not a major molecular event in gastric cancer occurring at early age, although the identification of a case with germline p.R337H mutation is consistent with the hypothesis that a small proportion of early, apparently sporadic gastric cancer, may be associated with widespread Brazilian founder mutations. Further studies are needed to evaluate the prognostic significance of markers for specific groups of patients according to tumor histology and familial history.展开更多
Adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)represent a heterogeneous group of diseases with distinct etiology,clinical features,treatment approaches,and prognosis.Studies are ongoing to ...Adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)represent a heterogeneous group of diseases with distinct etiology,clinical features,treatment approaches,and prognosis.Studies are ongoing to isolate molecular genetic subtypes,perform complete biological characterization of the tumor,determine prognostic groups,and find predictive markers to the effectiveness of therapy.Separate molecular genetic classifications were created for esophageal adenocarcinoma[The Cancer Genome Atlas(TCGA)],stomach cancer(TCGA,Asian Cancer Research Group),and colon cancer(Colorectal Cancer Subtyping Consortium).In 2018,isolation of TCGA molecular genetic subtypes for adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)highlighted the need for further studies and clinical validation of subtyping of gastrointestinal adenocarcinomas.However,this approach has limitations.The aim of our work was to critically analyze integration of molecular genetic subtyping of gastrointestinal adenocarcinomas in clinical practice.展开更多
文摘Early gastric carcinomas may develop with a molecular profile differing from sporadic carcinomas occurring at a later age. In this study, we analyzed a retrospective series of 88 patients with gastric adenocarcinoma diagnosed before the age of 45 years for the presence of TP53 mutations, clinicopathological features and immunohistochemistry to evaluate the expression of markers considered to be important in gastric carcinogenesis (E-cadherin, β-catenin, MUC1, MUC2, MUC5AC, MUC6 and p53). The majority of proportion of tumors were diffuse-type (70%) and advanced stage (56%). Familial history of cancer was positive in 21% of the cases. There was a significant association between altered expression of E-cadherin and β-catenin, and between p53 expression and perineural invasion. TP53 mutations were detected in 14.5% of evaluated cases, including a germline mutation (p.R337H) in a 12-year old patient. Overall survival analysis showed significant differences in relation with tumor stage and histopathology. The evaluated biomarkers did not present prognostic value in non-exploratory multivariate analyses. The low frequency of TP53 mutations in this series suggests these alterations are not a major molecular event in gastric cancer occurring at early age, although the identification of a case with germline p.R337H mutation is consistent with the hypothesis that a small proportion of early, apparently sporadic gastric cancer, may be associated with widespread Brazilian founder mutations. Further studies are needed to evaluate the prognostic significance of markers for specific groups of patients according to tumor histology and familial history.
文摘Adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)represent a heterogeneous group of diseases with distinct etiology,clinical features,treatment approaches,and prognosis.Studies are ongoing to isolate molecular genetic subtypes,perform complete biological characterization of the tumor,determine prognostic groups,and find predictive markers to the effectiveness of therapy.Separate molecular genetic classifications were created for esophageal adenocarcinoma[The Cancer Genome Atlas(TCGA)],stomach cancer(TCGA,Asian Cancer Research Group),and colon cancer(Colorectal Cancer Subtyping Consortium).In 2018,isolation of TCGA molecular genetic subtypes for adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)highlighted the need for further studies and clinical validation of subtyping of gastrointestinal adenocarcinomas.However,this approach has limitations.The aim of our work was to critically analyze integration of molecular genetic subtyping of gastrointestinal adenocarcinomas in clinical practice.
