Association of the immunohistochemical detection of gamma-glutamyl transferase expression with clinicopathological findings in postmenopausal women with endometrioid adenocarcinoma of the uterus.

Gamma-glutamyl transferase (GGT) is a membrane enzyme present not only in the liver but also in healthy endometrial epithelium. Its overexpression has been demonstrated in numerous malignancies, where it exerts an anti-apoptotic effect and causes drug resistance in response to oxidation stress. Aim of the study was investigation of GGT expression in postmenopausal patients with endometrioid adenocarcinoma of the uterus (EAC). The material comprised 98 paraffin-embedded post-operative tumour samples of EAC from postmenopausal patients and a control group of 60 normal human postmenopausal endometrium samples. For immunohistochemical specimen staining, polyclonal IgG anti-GGT was used; for GGT expression measurement, a semi-quantitative method was applied. In EAC patients, 16 (16.33%) were diagnosed as stage IA, 46 (46.93%) as stage IB, 14 (14.29%) as stage II, and 22 (22.45%) as stage IIIA-C, according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. Fifty-six (57.14%) patients were diagnosed with low- or moderate-grade (G1-2) disease, and 42 (42.86%) were diagnosed with high-grade (G3) disease. Cytoplasmic GGT staining was confirmed in all samples, while apical membrane GGT staining was observed only in G1-2 EAC specimens and the control group. In G3 EAC specimens, GGT cytoplasmic staining and high nuclear polymorphism areas were predominantly shown. Comparable high GGT median apical expression was confirmed in healthy endometrium (2.0, S.E.M. = 0.28) and in G1-2 EAC (2.0, S.E.M. = 0.27); however, in G3 tumours, GGT expression was significantly lower (0.0, S.E.M. = 0.07) than in healthy endometrium (P < 0.001 and P < 0.001, respectively). After stratification of the cancer cases according to FIGO staging, the lowest median apical GGT expression levels were in II EAC (0.0, S.E.M. = 0.64) tumours compared with IA (4.0, S.E.M. = 0.47) tumours, specimen and normal endometrium (2.0, S.E.M. = 2.8) (P < 0001). Stage IB EAC and IIIA-C EAC (1.0, S.E.M. = 0.16) cases showed only moderate median apical expression of GGT (1.0, S.E.M. = 0.24). We concluded that impaired GGT expression has the potential to become a valuable tool for stratifying EEC patients' prognosis and treatment planning.