Gamma-glutamyl transpeptidase immunoreactivity in benign and malignant breast tissue

GGT 129, a polyclonal antibody directed against gamma-glutamyl transpeptidase (GGT), was used to study GGT expression in formalin-fixed paraffin-embedded tissues from normal breast, 24 benign lesions, 27 in situ carcinomas or atypical hyperplasias, and 79 infiltrating mammary carcinomas. Epithelium of the ducts and ductules in normal breast tissue showed immunoreactivity along the apical surface. There was a strong correlation (P < 0.01) between the histologic classification of the tissue and GGT expression. All of the benign breast lesions stained positive for GGT. Among in situ carcinomas and atypical hyperplasias, 5/27 (19%) were negative for GGT while 22/27 were immunopositive. Infiltrating carcinomas showed the greatest deviation from normal tissue with 23/79 (29%) negative for GGT. GGT expression in benign and malignant breast tissue was not correlated with the age of the patient, suggesting that menopausal status does not influence expression of GGT. Correlation of GGT immunoreactivity with tubule formation, nuclear pleomorphism, mitoses, grade, size of tumor, lymph node status, and ER/PR status was performed for 69 cases of infiltrating ductal adenocarcinoma. There were no statistically significant relationships between the level of GGT immunoreactivity and any of the parameters. The loss of GGT in some of the cases is evidence that this enzyme is not required for mammary tumor development or maintenance. However, as GGT is a component of the pathways that metabolize glutathione and glutathione-conjugates, the difference in levels of the enzyme in invasive breast cancers may be one explanation for the variation in chemotherapy response that has been observed in patients treated for advanced mammary cancer.