Molecular characteristic of proximal and distal esophagogastric junction adenocarcinomas.

Abstract

e16077 Background: Esophagogastric junction adenocarcinomas (EGJA) are devastating diseases with increasing incidence. The 8th Edition TNM staging of American Joint Committeeon Cancer and Union for International Cancer Control defined that the epicenter of EGJA within 2 cm of the cardia (hereinafter referred to proximal EGJA) is staged according to the staging standard of esophageal cancer, while that more than 2 cm distal from the EGJA (hereinafter referred to distal EGJA) is staged according to the staging standard of stomach cancer. However, the rationality of the new definition in clinical practice is still controversial. Methods: A randomized retrospective study was conducted. Targeted next-generation sequencing of 450 cancer-related genes was performed, by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China, for genomic alteration identification. Results: A total of 198 EGJ patients were included in this study with a median age of 63 years (ranged from 39 to 88 years). Among them, 140 were distal EGJA and 58 were proximal EGJA. Genomic alterations with a high mutation frequency in EGJ include There is no significant difference in the frequencies of these genes between proximal EGJA and distal EGJA. Mutation frequencies of FGFR2 and ZEN217 in distal EGJ were significantly higher than those in proximal EGJA (15.8% vs 5.0%, P = 0.02 and 7.0% vs 0.7%, P = 0.03, respectively). Multivariate regression analysis showed that tumor stage and lymph nodes number were the main factors positively associated with the poor prognosis. However, we found that there was no significant difference in OS between proximal and distal (P = 0.139). Furthermore, our results showed that LRP2 and SPTA1 mutations were significantly associated with better OS of the EGJA patients. Conclusions: In conclusion, with the identification of the mutation landscape of EGJA, the FRFR2 and ZNF127 genes mutations were potential biomarkers to distinguish distal EGJA from proximal EGJA, whereas the LRP2 and SPTA1 gene mutations were potential biomarkers for prognosis prediction in EGJA.