Immunohistochemical differentiation of metastases of renal carcinomas versus other carcinomas with anti-gamma GT monoclonal antibody 138H11.

AIMS

Adenocarcinomas account for about 60% of metastatic cancers of unknown primary (CUP) site. In such a clinical CUP situation, histopathologists are challenged to differentiate renal cell carcinomas (RCC) from other adenocarcinomas with similar immunophenotypes, especially chemotherapeutically treatable mammary and ovarian carcinomas.

METHODS AND RESULTS

Recently, we produced a monoclonal antibody (mAb), designated 138H11, against human gamma-glutamyl-transferase (gamma GT), which stained over 98% primary clear cell and chromophilic RCC on frozen sections. The 138H11 epitope could not be stained using conventional techniques in most paraffin-embedded sections of the same origin, due to destruction by formalin fixation below the detection level. Here, we demonstrate that mAb 138H11 can specifically stain gamma GT in paraffin-embedded primary and metastatic RCC after enhancement with an ultrasensitive immunohistochemical method. We analysed a selected subgroup of adenocarcinomas with immunophenotypes which would not allow a differentiation from RCC in a CUP situation. We found a predominantly membranous expression of the 138H11 target antigen in 26/51 primary RCC and 15/ 34 metastatic RCC. In contrast, all 43/43 primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian, mammary, bronchial and gastric carcinomas were negative for mAb 138H11.

CONCLUSIONS

The data suggest that mAb 138H11 is useful for the immunohistochemical differentiation of RCC from other metastatic adenocarcinomas if the primary site of the tumour is not known.