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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, MUC<st1:chmetcnv w:st="on" tcsc="0" numbertype="1" negative="False" hasspace="False" sourcevalue="5" unitname="ac">5AC</st1:chmetcnv>, 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.<o:p></o:p> </p

journal of cancer therapy

Molecular Analyses of Early-Onset Gastric Cancer in Brazilian Patients: &amp;lt;i&amp;gt;TP&amp;lt;/i&amp;gt;53 Mutations, Cadherin-Catenin and Mucins Proteins Expression