Gamma-glutamyl transpeptidase immunoreactivity in benign and malignant breast tissue

GGT 129, a polyclonal antibody directed against gamma-glutamyltranspeptidase (GGT), was used to study GGT expression in formalin-fixedparaffin-embedded tissues from normal breast, 24 benign lesions, 27 in situcarcinomas or atypical hyperplasias, and 79 infiltrating mammary carcinomas.Epithelium of the ducts and ductules in normal breast tissue showedimmunoreactivity along the apical surface. There was a strong correlation (P< 0.01) between the histologic classification of the tissue and GGTexpression. All of the benign breast lesions stained positive for GGT. Amongin situ carcinomas and atypical hyperplasias, 5/27 (19%) werenegative for GGT while 22/27 were immunopositive. Infiltrating carcinomasshowed the greatest deviation from normal tissue with 23/79 (29%)negative for GGT. GGT expression in benign and malignant breast tissue wasnot correlated with the age of the patient, suggesting that menopausalstatus does not influence expression of GGT. Correlation of GGTimmunoreactivity with tubule formation, nuclear pleomorphism, mitoses,grade, size of tumor, lymph node status, and ER/PR status was performed for69 cases of infiltrating ductal adenocarcinoma. There were no statisticallysignificant relationships between the level of GGT immunoreactivity and anyof the parameters. The loss of GGT in some of the cases is evidence thatthis enzyme is not required for mammary tumor development or maintenance.However, as GGT is a component of the pathways that metabolize glutathioneand glutathione-conjugates, the difference in levels of the enzyme ininvasive breast cancers may be one explanation for the variation inchemotherapy response that has been observed in patients treated foradvanced mammary cancer.