Measurement of glutathione S-transferase P1-1 in plasma: pitfalls and significance of screening and follow-up of patients with gastrointestinal carcinoma.

Abstract

Gastrointestinal tumors often contain high amounts of the detoxification enzyme glutathione S-transferase P1-1 (GSTP1-1). Elevated levels of GSTP1-1 were found in serum and plasma from most patients with gastrointestinal tumors. The authors evaluated the role of GSTP1-1 as a plasma tumor marker in patients with gastrointestinal tumors. A sensitive and specific sandwich enzyme-linked immunoadsorbent assay for quantification of GSTP1-1 in human plasma was developed. GSTP1-1 levels in serum samples from 10 healthy controls were significantly (P < 0.0001) higher than in corresponding ethylenediaminetetraacetic acid (EDTA) plasma and varied with the type of blood collection tube used. Refrigeration or delayed centrifugation of blood collected in plain EDTA tubes resulted in spuriously high plasma GSTP1-1 levels. Therefore, all plasma samples were collected in silicone-coated EDTA tubes. The distribution of plasma GSTP1-1 levels in 230 blood donors was nearly normalized by logarithmic transformation and an upper normal reference level of 21.8 microg/L was calculated. Males had significantly higher (P < 0.0001) plasma GSTP1-1 levels than females and a significant increase (P < 0.004) in plasma GSTP1-1 with age was noted. In only 20 of 55 patients (36%) with gastrointestinal tumors was the plasma GSTP1-1 level above the upper normal reference limit. No significant decrease in plasma GSTP1-1 was noted in matched pairs of plasma samples collected from 17 patients before and at least 2 weeks after resection of the tumor. The GSTP1-1 level in serum and plasma depends on the materials and methods used to collect the samples. Only 36% of the patients with gastrointestinal tumors had elevated plasma GSTP1-1 levels that did not decrease after resection of the tumor. These findings argue against the use of GSTP1-1 as a serum or plasma marker for gastrointestinal tumors.