Serum soluble interleukin-2 receptor level as a prognostic indicator in gastric cancer.

B Nakata,K Hirakawa-Ys Chung,A Inui,Y Yamashita,M Sowa,N Onoda,Y Arimoto,K Maeda,T Sawada,Y Kato

doi:10.1038/bjc.1998.302

Abstract

T lymphocytes, activated by interleukin 2 during an anti-tumour response, release soluble interleukin 2 receptors (sIL-2R) into the bloodstream. We analysed the prognostic value of the serum sIL-2R level in gastric cancer. Serum concentration of sIL-2R in 96 gastric cancer patients and 100 healthy control subjects' was measured by enzyme-linked immunosorbent assay. All survivors were followed for more than 50 months. Serum sIL-2R level was considered with respect to prognosis, clinicopathological factors, other tumour markers and peripheral blood cell count. Stage III and IV patients had significantly higher sIL-2R levels than lower stage patients and control subjects. Stage III and IV gastric cancer patients were divided into 'high' and 'low' slL-2R groups based upon the control subjects' serum sIL-2R mean value plus one standard deviation. The high group had a significantly worse prognosis than the low group, although clinicopathological features and treatments were similar. Multivariate analysis demonstrated that the serum sIL-2R level is an independent indicator. The sIL-2R level did not correlate with carbohydrate antigen 19-9, however it did correlate with carcinoembryonic antigen (r = 0.22) and with numbers of peripheral blood monocytes (r = 0.54). In conclusion, serum sIL-2R may predict the outcome of gastric cancer patients with stage III or IV disease.

Highlights

PATIENTS AND METHODSPeripheral blood samples were obtained from each patient upon admission to the hospital and, after centrifugation, the serum samples were stored at - 20°C until assayed
There have been many studies on the serum soluble IL-2 receptor (sIL-2R) level in lung (Buccheri et al, 1991; Poulakis et al, 1991) and ovarian cancer patients (Barton et al, 1993, 1994; Gadducci et al, 1994), few studies have been reported on this cytokine receptor in the sera
When the sIL-2R concentration increases in the serum, it competes with the cell-surface 1L-2 receptor for binding to Interleukin 2 (IL-2) and it may reduce the availability of IL-2 for IL2-dependent immune responses (Rubin et al, 1985)

Summary

PATIENTS AND METHODS

Peripheral blood samples were obtained from each patient upon admission to the hospital and, after centrifugation, the serum samples were stored at - 20°C until assayed. Serum samples from 100 healthy individuals were used as controls. The survival period was defined as the interval from when the serum sample was obtained until 28 February 1997 for all living patients or until the day of death. A serum sample was added on a bead coated with a monoclonal antibody which relates to one epitope of sIL2R. Serum carcinoembryonic antigen (CEA) levels and carbohydrate antigen 19-9 (CA 19-9) levels were measured by counting immunoassay using a commercially available CEA kit (Ranream CEA; TOA Medical Electronics, Kobe, Japan) and a CA 19-9 kit (Ranream CA 19-9; Toray-Fuji Bionics, Tokyo, Japan). The white blood cell, lymphocyte and monocyte numbers were counted by a radio frequency/direct current detection method using an automated haematology analyser (SE-9000, TOA Medical Electronics, Kobe, Japan)

Statistical analysis

RESULTS

Lymphatic invasion

DISCUSSION

Hazard ratio