Y-Box-binding Protein-1 is a Potential Novel Tumour Marker for Neuroblastoma

Backround: The Y-box-binding protein-1 (YB-1) is a member of a family of DNA-binding proteins and an oncogenic transcription factor that is highly expressed in cancers of the breast, lung and prostate. To date, no data are available on its role in neuroblastoma. The aim of the present study was to evaluate the YB-1 expression in neuroblastoma. Materials and Methods: A tumour tissue microarray (TMA) was constructed from 36 neuroblastoma samples which were analysed by immunohistochemistry for YB-1 expression. Results: Expression of YB-1 was detected in 35 of 37 (94.6%) neuroblastoma cases examined. Nevertheless, no correlation of YB-1 expression with survival, risk factors or stage of the disease was observed. Conclusion: As the majority of neuroblastomas express YB-1, this protein may play an important role in tumour pathogenesis. The results of this study suggest that YB-1 may serve as a novel immune marker for neuroblastoma and may be potentially useful as a therapeutic target. Neuroblastoma is a childhood tumour which arises from sympathetic neuroblast cells derived from the neural crest. This tumour type is known to be the most frequent solid tumour in childhood outside the central nervous system (1, 2). Although overall survival of patients suffering from this tumour type is good, the prognosis of high-risk neuroblastoma patients is still poor, despite advances in diagnosis and treatment (3). It has been found that outcome correlates strongly with clinical factors such as age, stage and chromosomal aberrations (3). With the clinical application of prognostic markers, the therapeutic approach and clinical outcome was improved in these patients (4). Therefore it can be hypothesized that even more reliable markers may play a substantial role in the improvement of the treatment and diagnosis of neuroblastoma. The Y-box-binding protein-1 (YB-1) belongs to a family of Y-box proteins that bind DNA and RNA, and regulates gene expression through transcription and translation. YB-1 activates genes associated with cell proliferation and cancer development, such as matrix metalloproteinase-2 (MMP-2), multi-drug restistance 1 (MDR1), epidermal growth factor receptor (EGFR), cyclin B1 and cyclin A (5- 7). Genes associated with cell death, including the FAS cell death-associated receptor and p53, are repressed by YB-1. It has been shown that YB-1 is highly expressed in cancer of the breast (8), lung (9), ovary (10), bone (11), colon (12), thyroid (13), nasopharynx (14) and prostate (15) . Several reports indicate that YB-1 protein level and nuclear localisation is a prognostic marker for some types of human cancer (9, 16). To date, there are no published data regarding YB-1 expression in neuroblastoma. The aim of this study was to evaluate the expression of YB-1 in paediatric neuroblastoma by immunohistochemistry on a tumour tissue microarray and correlate the staining pattern with clinical outcome, survival, risk factors and disease stage.