The role of β-catenin and paired-like homeobox 2B (PHOX2B) expression in neuroblastoma patients; predictive and prognostic value

Abstract

BackgroundThe expression of β-catenin and paired-like homeobox 2B (PHOX2B) expression were assessed in Neuroblastoma (NB) patients as a diagnostic, prognostic and/or predictive markers. MethodsBone marrow (BM) samples of 52 NB patients were assessed for the expression of β-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. Resultsβ-catenin was expressed in 40 (76.92%) patients (P < .001). While PHOX2B was expressed in 32/52 (61.5%) patients, with a fold change of 0.29 (0.01–40.0, P = .096). β-catenin expression associated significantly with advanced tumor stage, high risk, positive results by MIBG and bone scan (P = .002, P < .001, P = .006, P = .013; respectively). Also it associated significantly with synaptophysin expression in the BM biopsy (P < .001), with a significant concordance (K = 0.519, P < .001). The expression of β-catenin associated significantly with PHOX2B gene expression [28/32 (87.5%), P = .04], and its fold change (P = .027), with a significant measure of agreement (K = 0.297, P = .022). The fold change of PHOX2B gene expression associated significantly with the high risk of the patients (P = .04). Poor response to treatment associated significantly with the expression of neuron specific enolase (NSE), β-catenin and PHOX2B in NB patients (P = .021, P = .019 and P = .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, P = .024). While with β-catenin (93.1%, 43.5%, 67.5%, 83.3%; respectively, P = .003), and PHOX2B expression (65.5%, 34.5%, 59.4%, 50%; respectively, P = .574). Conclusionβ-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.