MYCN amplification can serve as a favorable prognostic indicator for neuroblastoma

Neuroblastoma, a malignant tumor that primarily affects infants and young children, is a leading cause of death for children with cancer. When amplification of the MYCN oncogene is found in the tumor, it usually indicates an aggressive tumor with rapid progression of the disease and a poor outcome. Thus MYCN amplification has come to be used as a prognostic indicator.

However, sometimes a favorable outcome can be achieved even if MYCN amplification is present. A study reported in the current issue of the journal Pediatric and Developmental Pathology focuses on four such cases.

Four patients were diagnosed with neuroblastoma between the ages of 6 and 13 months and were treated with high-dose therapy and autologous stem cell rescue. Three of the patients are alive and well, having survived from 19 months to 7 years following treatment. One patient, with stage 4 disease, died eight months after being diagnosed.

Although MYCN amplification was confirmed in all four patients, it was not expressed in some of the common ways. Fluorescence in situ hybridization was used to identify the gene amplification in these cases. MYCN protein expression was not detected through immunohistochemistry.

Tumors with MYCN amplification typically have an undifferentiated or poorly differentiated subtype with a high mitosis-karyorrhexis index. Large cell type and presence of prominent nucleoli also characterize MYCN amplification and indicate aggressive behavior of the tumor. In the four cases examined in this study, the tumors all showed a poorly differentiated subtype and a low mitosis-karyorrhexis index. They also did not qualify as a large cell type and lacked prominent nucleoli.

These cases display a unique combination of unfavorable and favorable prognostic indicators for neuroblastoma. The authors speculate that a lack of excess MYCN protein expression despite gene amplification could cause this rare genotype-phenotype discordance. The findings could indicate that MYCN amplification does not automatically mean a poor prognosis.