GLUTATHIONE S-TRANSFERASES IN LIVER METASTASES OF COLORECTAL-CANCER -A COMPARISON WITH NORMAL LIVER AND PRIMARY CARCINOMAS

Glutathione S-transferase activity and levels of glutathione S-transfe rases-alpha, -mu and -pi were determined in 10 matched pairs of normal liver and liver metastasis from patients with colorectal cancer. For comparison, six matched pairs of colorectal cancer and normal mucosa w ere analysed. All metastases had a lower glutathione S-transferase act ivity when compared to the matched normal liver tissue (224 +/- 21 ver sus 900 +/- 95 nmol/min.mg protein respectively, P < 0.001). Mean acti vities in primary tumours and normal colorectal tissue were 176 +/- 22 and 150 +/- 13 nmol/min.mg protein respectively. When analysed by imm unoblot techniques, each metastasis contained less glutathione S-trans ferase-alpha than the surrounding normal liver (mean values 3.3 +/- 0. 8 versus 21.8 +/- 1.8 mu g/mg protein respectively, P < 0.001). Glutat hione S-transferase-alpha was undetectable in all primary tumours and normal colonic mucosa. Glutathione S-transferase-mu was detected in on ly two patients with liver metastases and in two patients with primary colorectal canter. All metastases contained more glutathione S-transf erase-pi than the surrounding normal liver tissue (3.7 +/- 0.5 versus 0.4 +/- 0.1 mu g/mg protein respectively, P < 0.001). The values in th e metastases were very similar to those in the primary colonic tumours (normal mucosa 2.3 +/- 0.3 and tumours 3.3 +/- 0.7 mu g/mg protein). Immunohistochemical investigation of the metastases revealed that glut athione S-transferase-alpha is not located in the malignant cells, but only in hepatocytes in what macroscopically seemed to be pure metasta tic tissue. Staining for glutathione S-transferase-pi reveals generall y positive tumour cells and, except for the biliary epithelium, only f aint staining of the hepatocytes. It is concluded that liver metastase s of colorectal carcinomas have very similar glutathione S-transferase enzyme activities and composition as compared,vith primary tumours.