Pyruvate kinase inhibition in the diagnosis of gliomas with an intermediate degree of malignancy

The aim of the investigation was to see if the histological diagnosis of brain tumors showing an intermediate degree of malignancy can be improved by the measurement of L-alpha-alanine inhibition of pyruvate kinase isoenzymes. The inhibition of pyruvate kinase activity was measured in 51 gliomas with different grades of malignancy. It was confirmed that benign tumors have a low level of inhibition (less than 50%) and that the more malignant the tumor, the higher the level of inhibition became, reaching more than 75%. However, when grade II and III astrocytomas and grade II and III oligodendrogliomas were analyzed, their level of inhibition was found to be variable. Grade II showed low and moderate levels of inhibition and grade III moderate and high levels. In turn, inhibition levels ranging from 50 to 75% were not only found in brain tumors with an intermediate grade of malignancy, but also in a number of benign and malignant tumors. When the survival times of patients with brain tumors were compared with both the histological diagnosis and pyruvate kinase inhibition, the prediction of the survival time on the basis of low and high levels of inhibition correlated well with the histological diagnosis. In contrast, when moderate levels of inhibition were measured, the prediction of the patients' survival remained uncertain and no improvement was found in the prediction for tumors showing an intermediate degree of malignancy on the basis of histology.