Immunohistochemical evaluation of a novel clone of monoclonal anti-MYCN antibody B8.4B in neuroblastic tumours: a correlation with MYCN gene status.
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Publications and source records attributed to Adela Cañete.
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Neuroblastoma (NB) is a pediatric cancer of highly variable clinical outcome. Much effort is devoted to detection of minimal residual (MRD) disease through RT-PCR or immunology of tissue-specific markers. Tyrosine hyrdroxylase (TH) has demonstrated a high utility to assess disease dissemination, although this marker can be lost due to clonal variability. Here we propose the use of the doublecortin (DCX) gene as a new molecular marker of neuroblastoma cells. DCX specifically appears in migrating neurons of the central and peripheral nervous system and interacts with and regulates the microtobule cytoskeleton. We have studied this gene by real-time quantitative RT-PCR in a total of 47 primary tumors and 202 samples of bone marrow or peripheral blood from 34 high-risk neuroblastoma patients as well as in 41 normal controls. The expression of DCX demonstrated a good specificity and concordance with TH, showing a higher expression rate in all the sample types studied as well as at different time points from diagnosis. We conclude that DCX would be a more efficient marker of minimal disease in neuroblastoma and perhaps other tumors of neuronal lineage.
Neuroblastoma is the most common solid tumour in childhood. Modern management includes a biopsy to perform genetic studies. Based on clinical data and Myc-N amplification (MNA), patients are divided in three prognostic groups: the low-risk (Stage 1, 2, 4S without MNA) has an event-free survival (EFS) of > 90% with surgery alone; the intermediate-risk (Stage 3, > 1 year of age, without MNA and Stage 3 and 4 infants without MNA) has an EFS of approximately 80% with mild chemotherapy and surgery; the high-risk group includes Stage 4, > 1 year of age and any stage and age with MNA. These patients are treated with chemotherapy, surgery, megatherapy, irradiation and 13-cis-retinoic acid. With this complex therapy, a 5-year EFS of 30-50% can be obtained.
Stage 4S neuroblastoma is a disease associated with spontaneous regression and good survival. We present a patient whose evolution has shown the variety and complexity of this disease in infants. Biologic factors, such as ploidy, MYCN copy number, loss of 1p36, and other chromosomal gains and losses were determined. A complex pattern of genetic abnormalities, such as near-diploidy, MYCN gain (2-4 copies per haploid genome) and imbalance/deletion of 1p36 was seen in the diagnostic sample. An extensive disseminated disease after a latent period of 26 months was associated with a special genetic evolution, such a tetraploidy, MYCN amplification (2:100-500 copies), 1p36 deletion, and gain of 17q. Our results provide evidence that either the primary tumor was heterogeneous in terms of gene amplification or that amplification was acquired later on as a transition from MYCN gain. We suggest that near-di-/tetraploid 4S tumors with MYCN gain and/or deletion 1p could be progressing 4S tumors.