Hanigan M H, Frierson H F, Brown J E, Lovell M A, Taylor P T
Department of Anatomy and Cell Biology, University of Virginia Health Sciences Center, Charlottesville 22908.
Cancer Res. 1994 Jan 1;54(1):286-90.
Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme that initiates the cleavage of extracellular glutathione, thereby providing the cell with the amino acids necessary for increased synthesis of glutathione. GGT is induced in ovarian tumor cell lines selected in vitro for resistance to cisplatin. No study has examined GGT expression in primary human ovarian tumors. We analyzed frozen sections of 80 normal human ovaries and 56 ovarian tumors for expression of GGT. Histochemical staining showed that GGT was not expressed in the cells of the follicle or surface germinal epithelium of the normal ovary. GGT was expressed in some epithelial inclusion glands and occasionally in a small subset of stromal cells. Granulosa-stromal cell tumors were largely GGT-negative. In contrast, GGT-positive neoplastic cells were observed in 33 of 45 common epithelial ovarian tumors. None of the patients had been treated with chemotherapy. Some of the tumors had only rare GGT-positive cells, while others consisted almost entirely of GGT-positive cells. Among the low malignant potential and invasive tumors, at least one-half of the cells were GGT-positive in 6 of 9 serous borderline tumors (2 with mucinous foci), 0 of 1 borderline mucinous tumor, 3 of 12 serous papillary carcinomas, 2 of 3 mucinous carcinomas, 1 of 2 endometrioid carcinomas, 2 of 2 clear cell carcinomas, 0 of 2 transitional cell carcinomas, and 4 of 5 undifferentiated carcinomas. There was no correlation between the stage of the tumor and GGT expression, indicating that a GGT-negative tumor does not become GGT-positive as it progresses to a more widely disseminated lesion. In addition, there was no correlation between serum levels of CA 125 and GGT expression. These data show that GGT is expressed in many common ovarian epithelial neoplasms. We are currently following the response of these patients to chemotherapy to determine if expression of GGT serves as a marker for identifying neoplasms with enhanced resistance to platinum-based therapy.
γ-谷氨酰转肽酶（GGT）是一种细胞表面酶，可启动细胞外谷胱甘肽的裂解，从而为细胞提供增加谷胱甘肽合成所需的氨基酸。在体外选择的对顺铂耐药的卵巢肿瘤细胞系中，GGT会被诱导产生。尚无研究检测原发性人类卵巢肿瘤中GGT的表达情况。我们分析了80例正常人类卵巢和56例卵巢肿瘤的冰冻切片中GGT的表达。组织化学染色显示，正常卵巢的卵泡或表面生发上皮细胞中不表达GGT。GGT在一些上皮包涵体腺中表达，偶尔也在一小部分基质细胞中表达。颗粒-间质细胞瘤大多为GGT阴性。相比之下，在45例常见的卵巢上皮性肿瘤中，有33例观察到GGT阳性肿瘤细胞。所有患者均未接受过化疗。一些肿瘤只有罕见的GGT阳性细胞，而另一些肿瘤几乎完全由GGT阳性细胞组成。在低恶性潜能和浸润性肿瘤中，9例浆液性交界性肿瘤（2例伴有黏液性病灶）中有6例、1例交界性黏液性肿瘤中0例、12例浆液性乳头状癌中有3例、3例黏液性癌中有2例、2例子宫内膜样癌中有1例、2例透明细胞癌中有2例、2例移行细胞癌中有0例以及5例未分化癌中有4例，至少一半的细胞为GGT阳性。肿瘤分期与GGT表达之间无相关性，这表明GGT阴性的肿瘤在进展为更广泛播散的病变时不会变为GGT阳性。此外，血清CA 125水平与GGT表达之间也无相关性。这些数据表明，GGT在许多常见的卵巢上皮性肿瘤中表达。我们目前正在跟踪这些患者对化疗的反应，以确定GGT的表达是否可作为识别对铂类疗法耐药性增强的肿瘤的标志物。
