Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification

The transcription factors of the Myb family are expressed in several tissue s and play an important role in cell proliferation, differentiation, and su rvival. In this study, the expression of A-myb, B-myb, and c-myb was invest igated in a group of 64 neuroblastomas at different clinical stages by a se nsitive reverse transcription-PCR technique and correlated with patients' s urvival. All of the myb genes were frequently expressed in neuroblastoma tu mors. Interestingly, the expression of B-myb, which was detected in 33 case s, was associated with an increased risk of death (P = 0.027 in a univariat e analysis), whereas there was no correlation with A-myb and c-myb expressi on. In addition, in a multivariate Cox regression analysis that included my b gene expression, MYCN status, age at diagnosis, and tumor staging, MYCN a mplification and B-myb expression were independently associated to an incre ased risk (P < 0.01 and P = 0.015, respectively). In overall survival curve s obtained by stratifying the neuroblastoma cases on the basis of MYCN stat us and B-myb expression, the group of patients without MYCN amplification a nd positive for B-myb expression had worse survival probability than that w ithout MYCN amplification and nonexpressing B-myb (P < 0.01). In summary, t hese findings provide the first demonstration that B-myb expression can be a useful prognostic marker in human neuroblastoma. Moreover, B-myb expressi on has a prognostic value complementary to MYCN amplification and can ident ify a group of high-risk patients that would not be predicted on the basis of the MYCN status only.