Tumor hypoxia has been implicated in treatment resistance and disease progression in esophageal squamous cell carcinoma (ESCC), yet its relationship with post-neoadjuvant pathological staging remains unclear. This study evaluated the association between hypoxia-inducible factor-1α (HIF-1α) expression and pathological stage following neoadjuvant concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 55 patients with ESCC treated with standardized neoadjuvant CCRT followed by curative esophagectomy. Immunohistochemical staining was performed on surgical specimens to assess tumor (HIF-T%) and stromal (HIF-N%) HIF-1α expression, and correlations with postoperative pathological stage were analyzed. Tumor HIF-1α expression was significantly higher in patients with pathological stage III disease compared with stage I–II disease (40% vs. 15%, p = 0.023). Increasing trends in tumor HIF-T% were observed across higher T and N classifications, although these did not reach statistical significance. Stromal HIF-1α expression was not associated with pathological stage. These findings demonstrate that elevated tumor HIF-1α expression is associated with advanced pathological stage following neoadjuvant CCRT in ESCC, supporting the role of hypoxia-related signaling in treatment resistance. HIF-1α may serve as a clinically relevant biomarker of residual disease burden, although further validation in larger cohorts is warranted.
Shih et al. (2026) studied this question.