Glutamate-L-cysteine ligase in breast carcinomas.
AIMS: 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. 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.[1]References
- Glutamate-L-cysteine ligase in breast carcinomas. Soini, Y., Karihtala, P., Mäntyniemi, A., Turunen, N., Pääkkö, P., Kinnula, V. Histopathology (2004) [Pubmed]
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