Gamma-Glutamyl Hydrolase (GGH) Overexpression in Luminal B Breast Cancer: A New Marker of Aggression and a Therapeutic Target

Introduction. Breast cancer is the most common malignant tumor in women, particularly in Algeria, where it ranks first in terms of incidence. It is classified into molecular subtypes (Luminal A, Luminal B, HER2, and Triple-Negative), which guide therapeutic decisions. Gamma-glutamyl hydrolase (GGH), an enzyme involved in folate metabolism, has been proposed as a biomarker in certain hormone-dependent cancers, but its role in breast cancer, especially the Luminal B subtype, remains poorly understood. This first Algerian study aims to evaluate the immunohistochemical expression of GGH in invasive breast cancer tissues and to analyze its correlation with clinicopathological features, particularly molecular subtypes. Materials and Methods. GGH expression was analyzed by immunohistochemistry on paraffin-embedded tissue samples, and the H-score was calculated based on the intensity and proportion of stained tumor cells. Results were correlated with clinicopathological parameters using the Chi-square test. Results. GGH overexpression was observed in 61.66% of cases, while 38.33% showed no expression. A significant association was found between GGH overexpression and estrogen receptor-positive tumors (89.18%, p = 0.011), high proliferation index (94.59%, p < 0.001) and the Luminal B molecular subtype (83.78%, p < 0.001). Conclusion. GGH expression is significantly increased in Luminal B breast cancers, suggesting its involvement in tumor progression. These findings highlight the potential of GGH as a prognostic biomarker and a promising therapeutic target, particularly for patients with the Luminal B subtype. Further studies are needed to validate these results on a larger scale and to explore the underlying molecular mechanisms.