Differential diagnosis of histogenetically distinct human epithelial renal tumours with a monoclonal antibody against γ-glutamyltransferase

Abstract

The localization of membrane-bound gamma-glutamyltransferase with monoclonal antibody (mAb) 138H11 proved to be of value for differential diagnosis of renal cancer, since it correlated with the histogenetic profile of human epithelial renal tumors. Immunoreactive gamma-glutamyltransferase was located in the proximal tubule in all normal human kidneys (15/15) examined thus far by both ultrastructural and immunohistochemical techniques. From 68 epithelial renal cancers tested 31/31 clear-cell carcinomas and 15/16 chromophilic carcinomas expressed the target epitope of mAb 138H11. In contrast, 0/11 oncytomas, 0/9 chromophobic carcinomas, and 0/1 Duct-Bellini carcinoma were immunoreactive. These results support a model of histogenesis and classification of epithelial renal tumours, according to which clear-cell and chromophilic renal carcinomas originate from transformed proximal tubule cells, whereas oncocytomas, chromophilic and Duct-Bellini carcinomas originate from cells of the collecting duct.

Immunoscintigraphic localization of renal tumours in an extracorporeal perfusion model with a monoclonal antibody against γ-glutamyltransferase

“…These tumours comprise the major portion of all malignant RCC. On the other hand, mAb 138H11 does not react with a histogenetically distinct group of renal tumours consisting of chromophobic carcinomas, Duct-Bellini carcinomas and oncocytomas [11]. In contrast to the apical localization in normal kidney cells, in RCC the 138H11 epitope is highly expressed on the outer membranes surrounding the tumour cells [ 11 ].…”

“…GGT is an enzyme normally expressed with highest specific activity in the proximal tubule brushborder membrane of the kidney [28,29] and it is also found as a variably glycosylated isoenzyme in renal cell carcinoma [10,14], where it may be involved in multidrug resistance [1]. Immunohistochemical analyses of human renal tissue sections with mAb 138Hll showed it to react strongly with 35/35 renal clear-cell carcinomas and 16/17 chromophilic carcinomas [11]. These tumours comprise the major portion of all malignant RCC.…”

“…We have recently produced and characterized a mAb (138Hll) against purified human 7-glutamyltransferase (GGT) [10,11]. GGT is an enzyme normally expressed with highest specific activity in the proximal tubule brushborder membrane of the kidney [28,29] and it is also found as a variably glycosylated isoenzyme in renal cell carcinoma [10,14], where it may be involved in multidrug resistance [1].…”

Hybridomas Reveal Shared Immunodominant Epitopes of γ-Glutamyltransferase Isoforms from Human Kidney and Renal Cell Carcinoma

“…This MAb reacted with all normal as well as RCC yGT isoforms [9,[13][14][15]. However, MAb 138H11 demon strated a different expression pattern of yGT on RCC cells compared to normal kidneys.…”

“…There, the 138H11 anti gen was expressed in large amounts on the outer membrane of the tumor cells ( fig. 1) [9,13]. Therefore, when human tumor-bearing kidneys were perfused in an extracorporeal system with radiolabelled MAb 138H11, a specific binding of circulating antibody to the tumor cells was demonstrated ( fig.…”