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Enlarged and prominent nucleoli may be indicative of MYCN amplification
A study of neuroblastoma (Schwannian stroma–poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index
Article first published online: 17 NOV 2004
Copyright © 2004 American Cancer Society
Volume 103, Issue 1, pages 174–180, 1 January 2005
How to Cite
Kobayashi, C., Monforte-Munoz, H. L., Gerbing, R. B., Stram, D. O., Matthay, K. K., Lukens, J. N., Seeger, R. C. and Shimada, H. (2005), Enlarged and prominent nucleoli may be indicative of MYCN amplification. Cancer, 103: 174–180. doi: 10.1002/cncr.20717
- Issue published online: 17 DEC 2004
- Article first published online: 17 NOV 2004
- Manuscript Accepted: 7 SEP 2004
- Manuscript Revised: 1 SEP 2004
- Manuscript Received: 20 MAY 2004
- Division of Cancer Treatment, National Cancer Institute. Grant Number: CA 13539
- International Neuroblastoma Pathology Classification;
- MYCN status;
- clinical characteristics;
According to the International Neuroblastoma Pathology Classification, neuroblastomas exhibiting MYCN amplification (A-MYCN) have unique histologic features—namely, undifferentiated/poorly differentiated subtype with a high mitosis-karyorrhexis index (U/PD-H). Nonetheless, certain tumors possessing these histologic characteristics contain a nonamplified MYCN gene (NA-MYCN).
The clinical characteristics of patients from the Children's Cancer Group (CCG) 3881 and 3891 studies who had neuroblastoma, U/PD-H, exhibiting A-MYCN (n = 68) or NA-MYCN (n = 33) were investigated. The histologic and cytologic features of tumors (A-MYCN, n = 62; NA-MYCN, n = 28) filed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, were reviewed, and nucleolar areas in undifferentiated neuroblastic cells were evaluated using image analysis methods.
All 68 patients whose tumors exhibited A-MYCN had disease that was in an advanced clinical stage (Stage III or IV); 89.7% of these patients were diagnosed between ages 0.5 and 3.5 years, and 67 of the 68 had been treated with the high-risk protocol in the CCG-3891 study. Children whose tumors exhibited NA-MYCN were evenly distributed across all age groups; 30 of these 33 children had advanced-stage disease, and 26 had been treated with a high-risk protocol. The prognosis associated with A-MYCN (event free survival [EFS], 15.7%; overall survival [OS], 22.2%) was significantly poorer than the prognosis associated with NA-MYCN (EFS, 56.1%; OS, 69.3%). The lone histologic/cytologic difference between tumors exhibiting A-MYCN and tumors exhibiting NA-MYCN involved nucleolar appearance. Neuroblastic cells in tumors exhibiting A-MYCN were characterized by the presence of 1 or more large, prominent nucleoli, and the mean nucleolar area was significantly greater in the 18 tumors exhibiting A-MYCN that were assessed (7.63 μm2) than in the 16 tumors exhibiting NA-MYCN that were assessed (5.53 μm2; P = 0.004).
Neuroblastomas, U/PD-H, were found to vary in terms of molecular background and clinical behavior. The results of the current study indicate that nucleolar enlargement in neuroblastic cells may be a sign of MYCN amplification. Cancer 2005. © 2004 American Cancer Society.