Creatine kinase and its isoenzymes in neoplastic disease

The CK-BB isoenzyme is ubiquitous in neoplastic tissue, but with low activity. Accordingly, it might be a nonspecific and insensitive tumor marker. Evaluation of BB isoenzyme in serum might indicate the extent of diseases or the response to therapy. The presence of CK-MB in patients with cancers may cause confusion with AMI. Serial determinations of both CK and lactate dehydrogenase isoenzymes are of great help in differential diagnosis. The presence of mit-CK is a poor prognostic sign in patients with malignancy. The greatest clinical significance of CK-BB and macro-CK isoenzyme lies in their effect on various assays for CK-MB. Macro-CK types 1 and 2 are much more heat stable than are CK-MB and CK-BB, and so by heating samples for 20 min at 45 degrees C the presence of thermostable macro types can be demonstrated. Macro-CK type 2 has a much higher activation energy than macro-CK type 1. If macro-CK is present, determination of the activation energy easily differentiates between types 1 and 2. CK-Bi seems to be glycosylated protein, and it is thought that glycosylation may be a general way of enzyme inactivation. If inactivation inside the cell is postulated, it has to be shown that enzymes indeed pass into the cell compartments where glycosylating enzymes are located. Another possible mechanism is within the circulation. Whether malignant cells themselves produce Ck-Bi or if inactivation occurs in the blood is still unknown. In this connection, one finding is that in plasma of cancer patients, CK-Bi can be reactivated to CK-BB by mercaptoethanol to 95%, whereas in plasma of normal persons there is no reactivation of the much lower CK-Bi concentrations.