L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases

Abstract

Using immunohistochemical and enzyme biochemical methods we investigated the expression of L- and M2-pyruvate kinase (PK) in normal renal tissue, renal cell carcinomas (RCCs; of clear cell, chromophilic cell and mixed cell type) and RCC metastases. L-PK was expressed in the proximal tubules of normal renal tissue and, to a variable extent, in 23/25 primary RCCs, in 1 RCC recurrence and in 10 RCC metastases. Staining intensity and percentage of stained tissue did not correlate with tumour grade. One renal oncocytoma and all extrarenal malignancies examined lacked L-PK immunoreactivity. M2-PK was mainly expressed in the distal tubules of the normal kidney and was found in all renal tumours as well as extrarenal malignancies. Quantitative biochemical investigations yielded a two- to seventeen-fold increase in PK activity in RCCs compared to the normal renal cortex taken from the same patient, whereas fructose-1,6-bisphosphatase and cytosolic glycerol-3-phosphate dehydrogenase activity was dramatically lower in RCCs. Otherwise, the activity of all other enzymes investigated (glucose-6-phosphate dehydrogenase, enolase and lactate dehydrogenase) was not significantly changed in the RCCs. The immunocytochemical results suggest that L-PK is a useful marker for RCC and its metastases, if acetone-fixed tissue is available. The quantitative changes of the concentration of PK and other enzymes in RCCs when compared with normal renal tissue probably reflect metabolic alterations related to tumour growth.