Basal-like subtype of esophageal adenocarcinoma and it's morphological, molecular and clinical characteristics

Esophageal adenocarcinoma (EAC) and squamous cell carcinoma are the two main tumor types of the esophagus, each with distinct morphological and molecular features. While mixed adeno-squamous carcinomas are recognized, it remains unclear whether a basal-like subtype-known from breast and pancreatic adenocarcinomas-also exists in EAC. This study analyzed tumor samples from 953 patients with operable EAC for expression of the basal cytokeratins CK5 and CK6. Tumors with any squamous differentiation were excluded. A small subset (3.4%) showed a basal-like phenotype, characterized by high CK5 and/or CK6 expression and small-luminal tubular growth. High CK5 expression was associated with significantly worse overall survival, and within the neoadjuvantly treated subgroup, it emerged as an independent negative prognostic marker. Tumors with concurrent high CK5 and CK6 expression also showed reduced survival. Exploratory analyses revealed potential associations between CK6 expression and Claudin18.2 status, and between CK5 expression and Y-chromosome loss. These findings indicate the presence of a distinct basal-like subtype within EAC, linked to poor prognosis and possible molecular differences. CK5, alone or in combination with CK6, may serve as a practical biomarker for identifying this subtype and could support the development of more personalized treatment strategies.