RESUMO
BACKGROUND: The expression of ß-catenin and paired-like homeobox 2B (PHOX2B) expression were assessed in Neuroblastoma (NB) patients as a diagnostic, prognostic and/or predictive markers. METHODS: Bone marrow (BM) samples of 52 NB patients were assessed for the expression of ß-catenin by immunohistochemistry (IHC), and PHOX2B by real time PCR (RT-PCR), compared to 12 healthy normal controls (NC). The data were correlated to the clinic-pathological features of the patients, response to treatment and disease relapse. RESULTS: ß-catenin was expressed in 40 (76.92%) patients (Pâ¯<â¯.001). While PHOX2B was expressed in 32/52 (61.5%) patients, with a fold change of 0.29 (0.01-40.0, Pâ¯=â¯.096). ß-catenin expression associated significantly with advanced tumor stage, high risk, positive results by MIBG and bone scan (Pâ¯=â¯.002, Pâ¯<â¯.001, Pâ¯=â¯.006, Pâ¯=â¯.013; respectively). Also it associated significantly with synaptophysin expression in the BM biopsy (Pâ¯<â¯.001), with a significant concordance (Kâ¯=â¯0.519, Pâ¯<â¯.001). The expression of ß-catenin associated significantly with PHOX2B gene expression [28/32 (87.5%), Pâ¯=â¯.04], and its fold change (Pâ¯=â¯.027), with a significant measure of agreement (Kâ¯=â¯0.297, Pâ¯=â¯.022). The fold change of PHOX2B gene expression associated significantly with the high risk of the patients (Pâ¯=â¯.04). Poor response to treatment associated significantly with the expression of neuron specific enolase (NSE), ß-catenin and PHOX2B in NB patients (Pâ¯=â¯.021, Pâ¯=â¯.019 and Pâ¯=â¯.040; respectively). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of synaptophysin for the diagnosis of BM metastasis in NB patients were (69%, 65.2%, 71.4%, 62.5%; respectively, Pâ¯=â¯.024). While with ß-catenin (93.1%, 43.5%, 67.5%, 83.3%; respectively, Pâ¯=â¯.003), and PHOX2B expression (65.5%, 34.5%, 59.4%, 50%; respectively, Pâ¯=â¯.574). CONCLUSION: ß-Catenin could be used as a sensitive and reliable marker for detection of BM metastasis and also a good predictor for resistance to treatment in NB patients. While, PHOX2B gene expression in BM aspirate could be a marker for high risk patients and poor response to treatment.