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Previous Volume 334:1505-1511 June 6, 1996 Number 23 Next

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ABSTRACT

Background Neuroblastoma is a heterogeneous disease, with manifestations ranging from spontaneous regression to lethal spread. Sometimes the tumor spontaneously differentiates toward a benign ganglioneuroma (maturing neuroblastoma). The prognosis is frequently related to ploidy, deletions in the short arm of chromosome 1, and amplifications of the N-myc oncogene. Maturing neuroblastomas consist of both neuronal cells and Schwann cells. We investigated the genetic composition of both cell types in maturing neuroblastomas, to determine the relation between genetic abnormalities and maturation.

Methods We studied 20 maturing and mature neuroblastomas by in situ hybridization to count the chromosomes and evaluate possible deletions in the short arm of chromosome 1 in neuronal and Schwann cells. The DNA content of the cells was measured by flow cytometry.

Results Neuroblastic and ganglionic cells showed aberrations in the number of chromosomes. In situ hybridization and flow cytometry demonstrated near-triploidy in 18 of 19 tumors and pentaploidy in the remaining tumor. The Schwann cells in all 20 neuroblastomas contained normal numbers of chromosomes. In 18 tumors studied, there were no chromosome 1 deletions in either type of cell.

Conclusions The Schwann cells in maturing neuroblastomas differ genetically from the neuronal cells. The normal number of chromosomes in Schwann cells and the abnormal number in neuroblastic and ganglionic cells suggest that Schwann cells are a reactive population of normal cells that invade the neuroblastoma. Near-triploidy of neuroblastoma cells and intact chromosome 1 are presumably genetic prerequisites for spontaneous organoid maturation, because we found no diploidy or chromosome 1 deletions in the neuronal cells of spontaneously maturing neuroblastomas.

Source Information

From the Children's Cancer Research Institute, St. Anna Kinderspital (I.M.A., A.Z., R.L., D.P., H.G., P.F.A.), and the Institute of Clinical Pathology, University of Vienna (I.M.A., G.A.), both in Vienna, Austria; and the Department of Pathology, Ulleval University Hospital, Oslo, Norway (B.R.).

Address reprint requests to Dr. Peter Ambros at the Children's Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria.

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