Glutamate-L-cysteine ligase in breast carcinomas

Aims : To investigate the immunohistochemical expression of the catalytic and regulatory subunits of γ-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.
Methods and results : 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.
Conclusions : 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.