Background Numerous studies have demonstrated that human epididymis protein 4 (HE4) is overexpressed in various malignant tissues including ovarian, endometrial, lung, breast, pancreatic, and gastric cancers. However, no study has examined the diagnostic impact of HE4 in patient with esophageal squamous cell carcinoma (ESCC) until now. Aim To analyze the value of four serum tumor markers for the diagnosis of ESCC, and examine the associations of serum levels of HE4 with ESCC patients' clinicopathological characteristics. Methods The case group consisted of 80 ESCC patients, which were compared to a control group of 56 patients with benign esophageal disease. Serum levels of HE4, carcinoma embryonic antigen (CEA), alpha fetal protein, and carbohydrate antigen 19-9 (CA19-9) were detected by ELISA. The associations of serum HE4 levels with ESCC patients' clinicopathological characteristics such as gender, tumor location, and pathological stage were also examined after operation. Results The result of ELISA showed that serum HE4 level was significantly higher in the patients with ESCC than in the controls, and the staining intensity was inversely correlated with the pathological T and N stages. Serum HE4 levels had a sensitivity of 66.2% and specificity of 78.6% when the cutoff value was set at 3.9 ng/mL. Moreover, the combined HE4 and CA19-9 increased the sensitivity to 83.33%, and interestingly, the combination of HE4 with CEA led to the most powerful sensitivity of 87.5%. Furthermore, A positive correlation was observed between HE4 serum levels and pathological T and N stages (P = 0.0002 and 0.0017, respectively), but there was no correlation between HE4 serum levels and ESCC patient gender (P = 0.4395) or tumor location (P = 0.6777). Conclusion The results of this study suggest that detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of ESCC.
