Elevation of the placental glutathione S-transferase form (GST-pi) in tumor tissues and the levels in sera of patients with cancer.

The content of glutathione S-transferase placental form (GST-pi) in colon and esophageal cancer tissues was determined by single radial immunodiffusion or activity inhibition tests. Average levels in colon adenomas and carcinomas were 163 +/- 38 and 143 +/- 30 micrograms/g, respectively, about 6-fold higher than the value of 25 +/- 4 micrograms/g observed for normal colonic mucosa. The content in esophageal cancer was similarly increased at 240 +/- 160 micrograms/g, about 6-fold higher than the level found in normal mucosa, 42 +/- 21 micrograms/g. The content was significantly higher in highly differentiated carcinoma (331 +/- 138 micrograms/g) than in moderately (205 +/- 123) or poorly (125 +/- 61) differentiated carcinomas, suggesting that GST-pi content seems to be related to the degree of differentiation of esophageal cancer. GST-pi was also expressed in cell lines derived from various cancers, including IMR 32, TE-9, and Ca Ski cells. The results thus indicate that GST-pi may be a useful marker for a wide range of cancers. An enzyme-linked immunosorbent assay developed to determine serum GST-pi content is described. Using this method GST-pi could be accurately measured in the range between 0.7 and 150 ng/ml, without interference of other isoenzymes. The serum GST-pi content was 1.3 +/- 1.2 ng/ml in 35 healthy controls and values of over 3.7 ng/ml (control mean + 2 SD) were found in patients with cancers of the stomach (10 of 23 cases), esophagus (26/43), bile duct (3/9), and colon (3/9), and in some leukemic cases. Although elevation of the serum content was not so often as that of tissue content, the fact that higher serum values of patients with esophageal cancer often reverted to the normal range after surgical removal of the cancer suggested a direct derivation of serum GST-pi from tumor tissues. Thus, follow-up of elevated serum GST-pi levels may be useful for monitoring cancer patients during the course of treatment.