Although the serum level of soluble interleukin-2 receptor alpha (sIL-2Ralpha) has been shown to correlate with progression and prognosis of several cancers, data to support its clinical significance to esophageal squamous cell carcinoma (ESCC) are limited. This study was conducted to assess the prognostic value and source of sIL-2Ralpha in patients with ESCC. From January 1986 to June 1997, 125 patients with histopathologically confirmed ESCC were enrolled for study. Ninety-three patients underwent en bloc esophagectomy, and 32 patients with unresectable tumor underwent palliative surgery. Four (4.3%; 4 of 93) patients died of surgical complications. Serum levels of sIL-2Ralpha were measured by ELISA. Expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma in the pathological section was determined, respectively, by immunohistochemistry (IHC) and in situ hybridization (ISH). Compared with the healthy control group (1020 +/-476 pg/ml, n = 103), ESCC patients tended to have significantly higher serum sIL-2Ralpha concentrations (1424 +/- 798 pg/ml, n = 121). The sIL-2Ralpha level was correlated with age, Tumor-Node-Metastasis classification, tumor stage, reading score of the IHC staining, and survival but not with the pathological grade or lymphovascular invasion. Prognosis was worse for patients with high sIL-2Ralpha levels (> or =1500 pg/ml) than for those with low serum sIL-2Ralpha levels (< 1500 pg/ml; P = 0.0209). It can be used as an independent prognostic factor of ESCC. In the pathological sections, expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma was detected in 17 (18.1%), 83 (89.2%), and 83 (89.2%) cases, respectively, by IHC, and the message of IL-2Ralpha was identified in tumor cells by ISH in 30.1% (28 of 93) of the cases. Serum concentrations of sIL-2Ralpha are frequently elevated in ESCC patients and are correlated with disease progression and survival. These data indicate that, in addition to activated T cells, cancer cells could be an important source of sIL-2Ralpha in ESCC patients.