The diagnostic and prognostic value of pretreatment serum creatine kinase BB levels in patients with neuroblastoma

Article Abstract:

Creatine kinase is an enzyme that aids in energy storage within some cells. The enzyme reversibly catalyzes the transfer of phosphate to the molecule creatine, where it remains in reserve until needed, at which point it may be transferred back to a molecule of adenosine diphosphate to form the high-energy adenosine triphosphate. The enzyme exists in several closely related forms, which are called isozymes. The isozyme designated BB, abbreviated CK-BB, is found in brain and smooth muscle, and a few other organs including lung, thyroid, and prostate. In the blood, creatine kinase is predominantly the M isozyme. Increases of serum creatine kinase BB may be indicative of tumor growth, and might therefore serve as a useful diagnostic marker. The potential use of this enzyme as a marker was investigated in patients with neuroblastoma. Neuroblastoma is the most common pediatric tumor, as well as being one in which prognosis is largely dependent upon the stage at diagnosis. If found to be spread at the time of diagnosis, it is usually fatal. The serum levels of 35 patients with neuroblastoma were compared with those in seven patients with rhabdomyosarcomas, five with hepatoblastomas, five with Wilm's tumors, two with yolk sac tumors, and one with a malignant thymoma, as well as with those of 47 hernia patients, who served as controls. The serum concentration of creatine kinase BB was found to be highly correlated with the outcome of treatment. The highest levels of CK-BB were found in patients with advanced stage IV disease. Eleven of 12 patients with levels of CK-BB above 15 nanograms per milliliter have died. In contrast, 8 of 10 patients with CK-BB below 11 nanograms per milliliter are alive and disease-free after two years. Although the normal CK-BB varies with age in children, the overall average is about 6 nanograms per milliliter. The serum concentration of CK-BB was elevated in only 60 percent of the patients, however. It is worth noting that although the mean CK-BB concentration was elevated among patients with more advanced disease, it remained a significant prognostic indicator even when only patients with advanced disease were considered. That is, elevated CK-BB levels are not merely an indicator of advanced disease, and in fact, patients with more advanced disease and lower CK-BB had better survival than patients with less advanced disease and higher CK-BB levels. The results suggest that creatine kinase-BB is a significant prognostic indicator in pediatric patients with neuroblastoma. (Consumer Summary produced by Reliance Medical Information, Inc.)

Creatine kinase, Cancer in children, Childhood cancer

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Stage IV neuroblastoma in infants: long-term survival

Article Abstract:

As is true for many cancers, the outcome for the childhood tumor neuroblastoma is strongly related to the stage of the disease. Stage IV neuroblastoma is advanced disease in which the cancer has spread to sites distant from the primary tumor. However, despite the fact that the overall picture for children with Stage IV neuroblastoma is quite grim, it has been observed that patients with Stage IV neuroblastoma who are younger than one year of age have a surprisingly good prognosis. The authors had originally presented the cases of 11 patients under one year of age with Stage IV neuroblastoma; they now extend their patient series to 24. The majority of patients received multi-agent chemotherapy consisting of nitrogen mustard, doxorubicin, cisplatin, cyclophosphamide, vincristine, and dacarbazine. The five-year survival without adverse events was 75 percent. Although only children with metastasis to the bone have died of neuroblastoma, 12 of 16 patients with metastatic spread to the bone continue to be free of disease. These survival rates are significantly better than those achieved by slightly older children. At the same institution, only 1 of 7 children with Stage IV neuroblastoma between 12 and 18 months of age was a long-term survivor, as was only 1 of 12 children between 18 and 24 months of age. There has been some suggestion that Stage IV neuroblastoma may be a biologically different entity among children younger than one year. The results with chemotherapy would seem to support that contention, yet the physiological reasons for this remain uncertain. Nevertheless, it is clear that improved long-term prognoses are enjoyed by advanced neuroblastoma patients who are under one year of age. Extremely aggressive procedures involving bone marrow transplantation are therefore not recommended for this group of patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Tumors in children, Pediatric tumors

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A significant association of Ha-ras p21 in neuroblastoma cells with patient prognosis: a retrospective study of 103 cases

Article Abstract:

Oncogenes are cellular genes that appear to be intimately involved in the regulation of cell replication and differentiation. Since these genes are often altered in cancer cells, they have become a great focus of research attention. A study was conducted to observe the expression of the Ha-ras gene in neuroblastoma cells. Neuroblastoma is a childhood cancer that is thought to arise during fetal life from cells of the sympathetic nervous system. Techniques of molecular biology were used to examine the Ha-ras genes in 32 specimens of neuroblastoma. No differences were observed among the various specimens. However, even though a gene is not altered, the expression of the gene, that is, the production of the gene product, may be. The gene product of the Ha-ras gene is a 21,000 molecular weight protein called simply Ha-ras p21. Using antibodies to this protein, it is possible to measure the amount of the protein, and by implication the gene expression, in a tissue specimen. Using such antibodies, the Ha-ras expression was evaluated in 103 specimens. Reduced ha-ras p21 was observed in 43 specimens. Thirty-six of the 43 patients (84 percent) died of aggressive neuroblastoma. In contrast, 17 of the 19 patients (89 percent) with large amounts of Ha-ras survived. Expression of the Ha-ras gene was found to be more common in earlier stages of neuroblastoma. Ninety-five percent of the patients with Stage I neuroblastoma expressed relatively high amounts of Ha-ras. In contrast, 59 percent of the patients with Stage IV neuroblastoma had little or no expression of Ha-ras. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Oncogenes, Ras genes

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