Mulder T P, Roelofs H M, Peters W H, Wagenmans M J, Sier C F, Verspaget H W
Department of Gastroenterology, University Hospital St Radboud, Nijmegen, The Netherlands.
Carcinogenesis. 1994 Oct;15(10):2149-53. doi: 10.1093/carcin/15.10.2149.
Glutathione S-transferase activity and levels of glutathione S-transferases-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 were analysed. All metastases had a lower glutathione S-transferase activity when compared to the matched normal liver tissue (224 +/- 21 versus 900 +/- 95 nmol/min.mg protein respectively, P < 0.001). Mean activities in primary tumours and normal colorectal tissue were 176 +/- 22 and 150 +/- 13 nmol/min.mg protein respectively. When analysed by immunoblot techniques, each metastasis contained less glutathione S-transferase-alpha than the surrounding normal liver (mean values 3.3 +/- 0.8 versus 21.8 +/- 1.8 micrograms/mg protein respectively, P < 0.001). Glutathione S-transferase-alpha was undetectable in all primary tumours and normal colonic mucosa. Glutathione S-transferase-mu was detected in only two patients with liver metastases and in two patients with primary colorectal cancer. All metastases contained more glutathione S-transferase-pi than the surrounding normal liver tissue (3.7 +/- 0.5 versus 0.4 +/- 0.1 micrograms/mg protein respectively, P < 0.001). The values in the metastases were very similar to those in the primary colonic tumours (normal mucosa 2.3 +/- 0.3 and tumours 3.3 +/- 0.7 micrograms/mg protein). Immunohistochemical investigation of the metastases revealed that glutathione S-transferase-alpha is not located in the malignant cells, but only in hepatocytes in what macroscopically seemed to be pure metastatic tissue. Staining for glutathione S-transferase-pi reveals generally positive tumour cells and, except for the biliary epithelium, only faint staining of the hepatocytes. It is concluded that liver metastases of colorectal carcinomas have very similar glutathione S-transferase enzyme activities and composition as compared with primary tumours.
