OA03-RF01.10. Distinct Clinical Roles of CK7/CK20 and CDX2 Expression in Esophagogastric Junction Adenocarcinoma

Abstract

Abstract Topic Esophageal Cancer: Esophageal Carcinogenesis Background Esophagogastric junction (EGJ) adenocarcinoma comprises tumors arising from distinct backgrounds, including Barrett’s esophageal adenocarcinoma and gastric cardia adenocarcinoma. Although CK7/CK20 expression patterns and CDX2 expression have been associated with intestinal differentiation and Barrett-related carcinogenesis, their relationships with tumor origin, lymphatic spread, and prognosis remain unclear. Methods A total of 82 patients who underwent curative surgery for EGJ adenocarcinoma were retrospectively analyzed. Immunohistochemical expression of CK7 and CK20 was evaluated using H-scores, and expression patterns were categorized by combined high/low profiles. CDX2 expression was classified as high or low using a predefined cutoff of 50% positive tumor cells. For tissue microarray (TMA) analysis, two cores per tumor were stained, and the mean expression value was used for analysis. Associations between marker expression, tumor origin estimated from pathological findings, mediastinal lymph node metastasis, and survival outcomes were investigated. Logistic regression adjusted for lymphadenectomy extent was used to estimate region-specific odds ratios for lymph node metastasis. Kaplan–Meier and Cox regression analyses were performed to evaluate overall survival (OS) and disease-free survival (DFS). Results Among the 82 patients, 60 were diagnosed with Barrett-related EGJ adenocarcinoma. CK7/CK20 expression patterns showed limited association with Barrett versus non-Barrett classification, although non-Barrett tumors tended to be more frequent in the CK7-high group (OR 2.33, p = 0.11) and the CK7/CK20 double-high group (OR 2.21, p = 0.33); however, these differences were not statistically significant. CDX2 expression was not associated with tumor origin. After adjustment for lymphadenectomy extent, high CDX2 expression (OR 1.38, p = 0.66) and high CK20 expression (OR 1.50, p = 0.77) tended to be associated with a higher frequency of mediastinal lymph node metastasis. In survival analyses, the CK7/CK20 double-high group demonstrated more favorable 5-year OS (p = 0.26) and DFS (p = 0.17) than the other CK7/CK20 expression groups. Furthermore, high CDX2 expression was associated with improved 5-year DFS (HR 0.62, p = 0.10), although the difference did not reach statistical significance. Conclusion In EGJ adenocarcinoma, CK7/CK20 expression patterns may partially reflect tumor phenotype, although they do not solely allow the accurate prediction of tumor origin. CDX2 expression does not appear to reflect tissue origin but may serve as a clinically useful biomarker for predicting mediastinal lymphatic spread and postoperative prognosis.