Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in Asia, particular in China. However, the pathogenesis of ESCC has not previously been well demonstrated. A major product of lipid peroxidation, 4-hydroxynonenal (4-HNE), is considered to be an oxidative stress inducer, as it is involved in the pathogenesis of a number of degenerative diseases, including Alzheimer's disease, atherosclerosis, cataracts and cancer. In order to investigate the association between oxidative stress and the pathogenic process of ESCC, the present study determined the expression levels of 4-HNE in 23 non-malignant esophageal epithelial tissues, 11 esophageal carcinoma in situ tissues and 57 ESCC tissues from patients in the Chaoshan area, a high-risk region for esophageal cancer in China. A significantly higher expression level of 4-HNE was identified in ESCC tissues compared with that in non-malignant esophageal epithelial tissues (P<0.05). Furthermore, immunohistochemical analysis demonstrated that expression levels of 4-HNE were significantly associated with the clinical stage. The patients with positive staining of 4-HNE revealed a poorer clinical outcome compared with that of patients with negative staining. 4-HNE was significantly associated with the severity of inflammation and increased with the progression of precancerous lesions (P<0.05). These results provide pathological evidence that oxidative stress is a driving force of ESCC carcinogenesis.