Related Experiment Video
Updated: Jan 16, 2026

Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Classification based on tumor phenotypes enables the novel molecular characterization of esophagogastric junction
Kyota Takahashi1,2, Keiichi Hatakeyama3, Masanori Terashima4
1Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan.
Background:
The incidence of esophagogastric junction (EGJ) cancer is increasing worldwide. Siewert type II EGJ cancer encompasses intestinal and gastric phenotypes; however, the molecular profiles and clinicopathological features remain unclear.
Methods:
Overall, 922 patients who underwent surgical resection for EGJ or gastric cancer from 2014 to 2023 were analyzed. The tumors were classified into intestinal and gastric phenotypes using immunohistochemistry. Molecular profiling was conducted using whole-exome sequencing, and clinicopathological features, mutational patterns, immune responses, and survival outcomes were investigated.
Results:
The intestinal phenotype exhibited frequent TP53 mutations and high NOX1 expression. High NOX1 expression was correlated with increased CD4 + and CD20 + lymphocyte infiltration. The intestinal phenotype was associated with better relapse-free survival (RFS) than the gastric phenotype. Metastatic patterns varied, with peritoneal and lymph node metastases being more common in the gastric and intestinal phenotypes, respectively. High NOX1 expression was an independent prognostic factor for RFS.
Conclusions:
EGJ cancers with intestinal and gastric phenotypes demonstrate distinct molecular and immune profiles that influence prognosis. The intestinal phenotype, characterized by TP53 mutations, high NOX1 expression, increased immune cell infiltration, and better survival outcomes, may impact EGJ cancer prognosis and could guide future diagnostic and therapeutic approaches.
Related Concept Videos
Barrett Esophagus-II: Clinical Manifestations and Management
To diagnose Barrett's esophagus, healthcare providers often recommend an endoscopy for those showing symptoms of acid reflux. The procedure...
Barrett Esophagus-I: Introduction
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...
Classification of Epithelial Tissues: Overview
Based on the number of cell layers,...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Classification of Epithelial Tissues: Stratified Epithelium

