Cellular DNA Content as a Predictor of Response to Chemotherapy in Infants with Unresectable Neuroblastoma

Abstract

We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with 2 of 25 (P = 0.003). Of 17 evaluable patients with unresectable hyperdiploid tumors, 15 had complete responses and two had partial responses to cyclophosphamide and doxorubicin; six others with diploid tumors did not respond (P = 0.00001). We also found that each of the four infants with Evans' Stage IV-S neuroblastoma, an unusual form of disseminated neuroblastoma with a relatively good prognosis, had hyperdiploid tumor cells of clonal origin. We conclude that in neuroblastoma of infants, hyperdiploidy of tumor cells is associated with a better response to chemotherapy than is diploidy.

Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

“…Sporadic neuroblastomas show a worse outcome as compared with neuroblastomas detected by mass screening that is currently being carried out in Japan (Sawada, 1986). Neuroblastomas with diploidy or tetraploidy show a worse prognosis than those with hyperdiploidy or pentaploidy (Look et al, 1984). In addition, the outcome in patients of older than 1 year is worse compared with in patients of younger than 1 year (Fortner et al, 1968).…”

Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature

“…On the other hand, the majority of sporadic neuroblastomas are discovered at advanced stages, and their prognosis is still very poor (Brodeur, 2003;Schwab et al, 2003). Recently advanced cytogenetic analyses revealed that given subsets of neuroblastomas with a favorable prognosis possess the hyperdiploid karyotype of chromosomes (Look et al, 1984;Tomioka et al, 2003) and that the other subsets with an unfavorable prognosis usually possess the diploid or tetraploid karyotype and often have MYCN amplification, gains of chromosome arms 1q, 2p and 17q, as well as allelic losses of chromosome arms 1p, 3p and 11q (Brodeur, 2003;Schwab et al, 2003). We and other investigators have previously reported the high accuracy of geneexpression profiling to predict the prognosis of neuroblastoma (Wei et al, 2004;Ohira et al, 2005).…”

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

“…1,2 A number of prognostic parameters for the disease have been identified, including age, loss of heterozygosity at chromosome 1p36, DNA ploidy, histopathologic stage and amplification of the N-myc proto-oncogene. [3][4][5][6][7][8] The latter condition is strongly correlated with advanced disease, insensitivity to chemotherapy and poor outcome. 9 -12 N-myc and other members of the myc family encode transcription factors that control the expression of genes involved in cell growth, differentiation and survival.…”