Abstract
Hypoxia-inducible factor (HIF-1α) is the initial switch in angiogenesis; however, its expression in superficial esophageal carcinoma is unclear. We determined the timing of the hypoxia-induced angiogenesis switch by investigating the expression of HIF-1α and the erythropoietin (Epo) it activates in superficial esophageal carcinoma. We used 53 lesions of superficial esophageal carcinoma and conducted immunohistochemistry of HIF-1α and Epo. Cases were divided into three groups: T1a-EP/LPM (22 lesions), T1a-MM/T1b-SM1 (15 lesions), and T1b-SM2,3 (16 lesions). We compared HIF-1α and Epo expression in the deepest area and examined the correlation between HIF-1α and Epo scores. In 24 cases of T1a-MM or deeper carcinomas with intraepithelial spread, we compared HIF-1α and Epo scores in the intraepithelial spread and deepest areas in the same cases. Both HIF-1α and Epo were most strongly expressed in T1a-EP/LPM, with significant attenuation at T1a-MM and deeper. Both HIF-1α and Epo had significantly higher scores in the T1a-EP/LPM group than in the T1a-MM/T1b-SM1 and T1b-SM2,3 groups. HIF-1α and Epo were strongly correlated, and were significantly higher in intraepithelial spread areas than in invaded areas. HIF-1α and Epo are strongly expressed from an early stage of esophageal carcinoma; as the carcinoma invades the muscularis mucosae and deeper, expression decreases.