Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young patients. Here, we report such a case in a 29-year-old Chinese man.

This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation. Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line, without Barrett's esophagus or involvement of the gastric cardia. The nodule was completely resected by endoscopic submucosal dissection (ESD). Pathological examination confirmed diagnosis of intramucosal adenocarcinoma mixed with an NEC component, measuring 1.5 cm. Immunohistochemically, both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%; NEC was positive for synaptophysin and chromogranin. Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene, a common gastric cancer driver gene, in addition to pathogenic somatic mutations in P53 and CHEK2 genes. The patient was alive without evidence of the disease 36 mo after ESD.

Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

Despite investigations into microRNA (miRNA) expression in esophageal cancer (EC) tissue, miRNAs that participate in EC pathogenesis and their subsequent mechanisms of action remain to be determined. The present study aimed to identify important miRNAs that contribute to EC development, and to assess miRNA biomarkers that could be used in EC diagnosis, prognosis and therapy. Bioinformatics analysis was performed to reanalyze EC tissue miRNA expression microarray dataset GSE113776, which was followed by in vitro verification of miRNA functions using reverse transcription‑quantitative PCR, western blot analysis and a dual‑luciferase reporter assay. Out of 93 miRNAs extracted, only miR‑200a was significantly increased in EC tissues. Transfection of KYSE150 esophageal squamous cell carcinoma (ESCC) cells with miR‑200a mimics significantly increased their proliferative, migratory and invasive ability, whereas the opposite cell behaviors were observed in ESCC cells transfected with a miR‑200a inhibitor. A total of six miR‑200a target genes [catenin β1 (CTNNB1), cadherin‑1 (CDH1), PTEN, adenomatous polyposis coli (APC), catenin α1 (CTNNA1) and superoxide dismutase 2 (SOD2)] were selected for further analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein‑protein interaction network map data and protein expression in esophageal tissue. These target genes were downregulated under miR‑200a expression and upregulated in the presence of the miR‑200a inhibitor. The association between miR‑200a and the 3'‑untranslated region of target genes in ESCC cells was confirmed using a dual‑luciferase reporter assay. In conclusion, the present study demonstrated that miR‑200a may participate in the promotion of ESCC cell proliferation, migration and invasion, and provided novel evidence for the direct interaction between miR‑200a and CTNNB1, CDH1, PTEN, APC, CTNNA1 and SOD2, which may contribute to the observed altered cell behavior.