Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

Abstract

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy (1.35±0.28 vs 1.25±0.23, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42±0.28, 16.5%, n=56), followed by lung cancer (1.38±0.24, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies (1.44±0.41)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage (1.37±0.26 vs. 1.29±0.31, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis (1.48±0.30 vs. 1.30±0.21, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

Unexplained Extremely High Creatine Kinase-MB Levels in a Cancer Patient with No Chest Pain

“…Most often, its components entail CK-BB and monoclonal IgG. 2,3 All except macro CK type 2 consist of a normal enzyme complexed with an immunoglobulin, most commonly IgG or IgA. The complexed enzyme has reduced blood clearance, resulting in increased circulating amounts of the higher-than-normal molecular weight form of the relevant enzyme.…”

“…Thus, this amalgamated molecule may interfere with commonly used biochemical assays by adding to the estimation of CK-MB but not to the total CK.7 Conversely, high levels of total CK with a normal CK-MB have also been described in the literature. 2,4 Irrespective of the macro-CK subtype, a retrospective study by the Change et al, concluded that approximately 40% of the patients with the CK-MB: total CK ratio greater than the 1 had the underlying malignancy.…”

Creatine Kinase-MB measurement using Immunoinhibition methodology. How much is the interference?

“…Therefore, the three different cytosolic isoenzymes formed by the various combinations of M (muscle) and B (brain) subunits in the cytosol are-CK-MM, CK-MB and CK-BB. [1][2][3][4][5][6] The CK-MM is mainly found in all kinds of muscle cells, CK-MB mainly in the myocardial cells and CK-BB exists mainly in the brain cells. 3 The distribution of various isoenzymes in the serum of healthy individuals is:-CK-MM (96-100%), CK-MB (0-6%) and CK-BB is almost undetectable.…”

“…3 The distribution of various isoenzymes in the serum of healthy individuals is:-CK-MM (96-100%), CK-MB (0-6%) and CK-BB is almost undetectable. 6 Apart from these cytosolic enzymes, a mitochondrial isoenzyme of CK (CKm) is found in muscle, brain and cerebrospinal fluid. 2 The creatine kinase isoenzyme CKMB is cardio-specific and is accepted as the most sensitive and specific indicator of myocardial cell necrosis.…”

Intravenous cannula can increase serum creatine kinase MB activity

“…In some cases, CK-MB activity measured using an immunoinhibition technique may exceed the upper-normal limit, whereas CK-MB mass measurements of the same sample may be in the normal range. Many laboratories still use immunoinhibition as the routine method to measure CK-MB activity in serum for several reasons [4,5]. In Izmir, the third largest city in Turkey, about 100.000 CK-MB activity tests per year are performed in 15 different state hospitals.…”