Microenvironment and Biomarkers in Esophageal Cancers: An Approach for Early Detection and Identification

Background Esophageal cancer is a prevalent and highly lethal malignancy worldwide, comprising two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While both subtypes are frequently encountered, ESCC has historically been more common globally. However, in recent decades, EAC has emerged as the predominant type in industrialized nations, often developing from Barrett's esophagus, a condition driven by chronic gastroesophageal reflux disease (GERD). ESCC typically occurs in the upper esophagus, whereas EAC arises near the lower gastroesophageal junction. The etiology of esophageal cancer is multifactorial, with diverse causes and clinical management strategies. Notably, diagnosing tumors located in the lower esophagus presents significant challenges. EAC is particularly prone to diagnostic errors, as it can be mistaken for ESCC. This study aims to investigate potential histological biomarkers for EAC to facilitate early and accurate identification of histological changes, especially in patients with GERD. Methods This cross-sectional study examined archival histological samples from patients with lower esophageal abnormalities. Immunohistochemistry was used to investigate the P63 marker, while Masson's trichrome stain was employed to evaluate cancer progression and associated microenvironmental changes. Results A total of 104 cases were analyzed, including 13 with known P63-positive staining and five P63-negative controls. The remaining cases consisted of both precancerous and cancerous tissues diagnosed as EAC. Among these, 86 cases showed negative P63 staining, confirming their origin from non-squamous cells and supporting their classification as true Barrett's-related epithelium. In contrast, five of the 13 SCC control cases exhibited P63 positivity, demonstrating a highly significant association (p < 0.00001). Additionally, Masson's trichrome staining revealed stromal collagen fibers infiltrating the malignant tissue areas. Conclusions This study highlights the significance of the P63 marker in distinguishing between ESCC and EAC. It also suggests a potential role for Masson's trichrome stain in identifying early microenvironmental changes associated with EAC progression.