Loss of avidin-binding activity in renal cell carcinoma
Antineoplastic Combined Chemotherapy Protocols
Lymph Node Excision
Neoplasms, Germ Cell and Embryonal
Avidin is a basic glycoprotein with a very strong affinity for biotin, a vitamin that serves as the active prosthetic group of several enzymes in human metabolism. Biotin distribution in the normal kidney and in renal cell carcinoma was determined by histochemical examination of peroxidase labelled avidin binding in 15 normal human kidney specimens and 50 kidney tumors. All normal kidneys examined showed intense granular cytoplasmic binding of avidin by the proximal tubular cells. Oncocytomas (5/5) showed uniformly very intense cytoplasmic avidin-binding activity throughout both solid and tubular areas. However, only 4/45 (9%) renal cell carcinomas stained uniformly for labelled avidin. These 4 tumors were primarily papillary on histologic examination. Heterogeneous staining was noted in 8/45 (18%) renal tumors. Most renal cell carcinomas, 33/45 (73%) did not show any avidin-binding activity. Human renal cell carcinoma is characterized by reduced gluconeogenesis, which is regulated by pyruvate carboxylase, a biotin-dependant enzyme. Our data suggest that the decrease or absence of avidin-binding activity in renal cortical tumors may reflect the decreased biotin requirement of alternate metabolic pathways in neoplastic cells that do not include biotin dependant enzymes. Alternatively, the loss of biotin may be a primary event in malignant transformation resulting in decreased activity of biotin dependant enzymes, such as pyruvate carboxylase. Whether this results from inactivation of biotin transport mechanism(s) or the decrease of biotin receptors remains to be determined.