Adenocarcinoma of the esophagogastric junction and its background mucosal pathology: A comparative analysis according to Siewert classification in a Japanese cohort

Abstract

Adenocarcinoma of the esophagogastric junction (AEG) has heterogeneous carcinogenic process due to its location straddling the esophagogastric junction. We assessed background mucosal pathology and its correlation with clinicopathological features of each Siewert type of AEG. Clinicopathological and immunohistochemical analyses of 103 AEGs and 58 gastric cancers (GCs) were conducted. Background mucosal features were evaluated according to the updated Sydney System. Siewert classification divided 103 AEGs into three type I, 75 type II, and 25 type III tumors, respectively. Two type I, 9 type II AEGs, and none of type III AEGs were Barrett-related and were excluded from further analysis. Background mucosa of type III AEGs more frequently showed moderate to marked degree of atrophy and intestinal metaplasia than those of type II AEGs and was very similar to those of GCs. Among type II AEGs, tumors with atrophic background were significantly associated with higher patient age and intestinal-type histology. Type II AEGs with nonatrophic background, but not those with atrophic background, showed more frequent mismatch repair deficiency, TP53 overexpression, and less frequent intestinal phenotypic markers expression than type III AEG or GC. Type II AEGs with atrophic background involved suprapancreatic nodes more frequently than those without. We demonstrated that chronic atrophic gastritis was a major precancerous condition of AEG in the Japanese population, especially Siewert type III which had background mucosal pathology similar to that of GC. Type II AEGs with and without atrophic background showed some clinicopathological differences, and these observations might represent heterogeneous carcinogenic process within type II AEGs.

Keywords: Barrett's cancer; Siewert classification; adenocarcinoma; esophagogastric junction; gastric cancer.

Figure 1

Histologic evaluation of background mucosa adjacent to AEG. A, A 10 mm longitudinal range of glandular mucosa on the lesser curvature immediately adjacent to the anal side of the primary tumor (arrow) was histologically evaluated. E, proximal esophageal squamous epithelium; T, tumor; G, distal gastric epithelium as mucosal background. B, Microscopic appearance of the evaluated area

Figure 2

A, Background mucosal type of 103 AEGs and 58 GCs was divided into six categories. B, Background mucosal pathologies of 91 AEGs (excluding 11 Barrett‐related cancers and one cancer associated with the esophageal proper glands) and 58 GCs were evaluated in accordance with the updated Sydney System. Degrees of atrophy, intestinal metaplasia, and neutrophilic and mononuclear cell infiltrations were divided into four grades

Figure 3

Survival analysis using Kaplan‐Meier methods. Dichotomous comparisons of overall survival among 66 type II AEG patients (excluding those with Barrett‐related cancers) according to grades of atrophy/intestinal metaplasia of the background epithelium (“atrophic” vs “non‐atrophic”)

Figure 4

The distribution of lymph node metastases in Siewert type II cancers. A, Node‐positive tumors with a “non‐atrophic” background (n = 20). B, Node‐positive tumors with an “atrophic” background (n = 19). Pie charts for each lymph node station indicate the proportion of node‐positive/negative cases: Black represents node‐positive cases and white node‐negative cases, with numbers of cases. Lymph node stations are defined as follows: “Lower mediastinal” station includes lower thoracic paraesophageal, supradiaphragmatic, and posterior mediastinal nodes; “Parahiatal” station includes infradiaphragmatic nodes and nodes along the esophageal hiatus; “Suprapancreatic” station includes nodes along the left gastric artery, common hepatic artery (anterosuperior side), the celiac artery, splenic hilum, and the splenic artery; “Perigastric” station includes right cardial, left cardial, lesser curvature, suprapyloric, and infrapyloric nodes as well as the nodes along the short gastric artery, the left gastroepiploic artery, and the right gastroepiploic artery