Glutamate-L-cysteine ligase in breast carcinomas

Abstract

To investigate the immunohistochemical expression of the catalytic and regulatory subunits of gamma-glutamyl cysteine synthetase, i.e. glutamate-L-cysteine ligase (GLCL) in 274 invasive and in-situ breast carcinomas. GLCL is the rate-limiting enzyme in glutathione synthesis, which is one of the most important intracellular antioxidants participating in the detoxification reactions of several cytotoxic drugs. In the tumour cells GLCL reactivity was observed in 50% and 44% of the cases for the catalytic and the regulatory subunits, respectively. There was a statistically significant association between their expression (P = 0.002). Lobular invasive carcinomas expressed the catalytic and regulatory subunits more often than other tumours (P = 0.050 and P = 0.046, respectively). Also in-situ carcinomas expressed the catalytic subunit more often (P = 0.005). Tumours showing no immunoreactivity for the catalytic subunit had axillary metastases significantly more often (P = 0.013). Patients with tumours showing positivity for either subunit or both had a better survival (P = 0.037). No difference in survival could be observed between GCLC-positive or -negative cases in the subgroup receiving chemotherapy. Expression of the catalytic and regulatory subunits of GLCL is found in a substantial number of breast carcinomas and their expression is more pronounced in lobular invasive and in-situ carcinomas. Even though the overall expression of GLCL was associated with improved survival, no such effect was observed separately in the group receiving chemotherapy.