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Expression of B-myb in Neuroblastoma Tumors Is a Poor Prognostic Factor Independent from MYCN Amplification¹

ENEA CR Casaccia, Section of Toxicology and Biomedical Sciences, 00060 Rome, Italy [G. R., V. C., R. A., A. N., B. T., P. A.]; Unit of Solid Tumor Biology, Advanced Biotechnology Center, Genoa, Italy [G. P. T.]; G. Gaslini Institute, IV Pediatric Division, 16100 Genoa, Italy [B. D. B.]; and Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [B. C.]

The transcription factors of the Myb family are expressed in several tissues and play an important role in cell proliferation, differentiation, and survival. In this study, the expression of A-myb, B-myb, and c-myb was investigated in a group of 64 neuroblastomas at different clinical stages by a sensitive reverse transcription-PCR technique and correlated with patients’ survival. All of the myb genes were frequently expressed in neuroblastoma tumors. Interestingly, the expression of B-myb, which was detected in 33 cases, was associated with an increased risk of death (P = 0.027 in a univariate analysis), whereas there was no correlation with A-myb and c-myb expression. In addition, in a multivariate Cox regression analysis that included myb gene expression, MYCN status, age at diagnosis, and tumor staging, MYCN amplification and B-myb expression were independently associated to an increased risk (P < 0.01 and P = 0.015, respectively). In overall survival curves obtained by stratifying the neuroblastoma cases on the basis of MYCN status and B-myb expression, the group of patients without MYCN amplification and positive for B-myb expression had worse survival probability than that without MYCN amplification and nonexpressing B-myb (P < 0.01). In summary, these findings provide the first demonstration that B-myb expression can be a useful prognostic marker in human neuroblastoma. Moreover, B-myb expression has a prognostic value complementary to MYCN amplification and can identify a group of high-risk patients that would not be predicted on the basis of the MYCN status only.

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