Aberrant bcl-2 and bax protein expression related to chemotherapy response in neuroblastoma

Neuroblastoma (NB) is a tumor of the sympathetic nervous system which develops in young children. It derives from cells of the embryonal neural crest that form many different tissues, including the adrenal medulla and the sympathetic ganglia. Survival rates for patients with neuroblastoma have remained unchanged despite intensive efforts to develop more effective treatment strategies. The intrinsic resistance of many tumor types to antineoplastic therapies and the appearance of resistant cell populations upon relapse of an originally responsive tumor represent major impediments to successful treatment. The possibility exists that these neoplasms, particulary those that have become refractory to chemotherapeutic drugs, may occur in part because of failed apoptosis. In this study we investigated the immunocytochemical expression, before and after a trial of chemotherapy of the bcl-2 and bax proteins in 15 cases of NB, including 8 stroma-poor and 7 stroma-rich NBs. Patients with strong expression of bcl-2 before the treatment had shorter survival than those with weak or moderate expression of the protein (p = 0.004). Moreover, bcl-2 protein expression was correlated to the stroma-poor histotype only after the treatment (p = 0.031). An association between bax protein expression before treatment and longer survival (p = 0.014) was also found. We conclude that bcl-2 and bax expression, before the treatment, could be of prognostic value in neuroblastomas.