Correlation of modified Shimada classification with MYCN and 1p36 status detected by fluorescence in situ hybridization in neuroblastoma

Abstract

Neuroblastoma (NB) is a childhood cancer derived from neural crest cells, with a highly variable clinical course and biologic behavior. NB cells harbor complex genetic changes. Also, MYCN amplification is a well-known molecular marker for aggressive progression, and deletion of the short arm of chromosome 1 is frequently observed in NB. The aim of this study was to investigate the correlation between genetic markers and prognostic morphological parameters to address the biology and underlying the clinical complexity of NB. Therefore, we performed fluorescence in situ hybridization analyses of chromosome band 1p36 and MYCN in a series of tumors from 43 cases classified according to the recommendation of International Neuroblastoma Pathology Committee (modification of Shimada classification). The correlations of MYCN amplification status and two distinct types of 1p36 alterations (deletion and imbalance) with Shimada classification and histologic prognostic factors were statistically analyzed. Amplification of MYCN and 1p36 deletion was present in 14 (32.6%) and 18 (41.9%) cases, respectively. Sixteen cases (37.2%) displayed a favorable histology, while 27 (62.8%) had an unfavorable histology. The 1p36 deletion was found to be an independent predictor of unfavorable histology by multivariate analysis (logistic regression test, P = 0.03), but the 1p36 imbalance did not show any significance. Both 1p36 deletion and MYCN amplification showed significant correlation with undifferentiated tumors (chi-square test, P = 0.002 and 0.03, respectively). Highly significant correlation was found between the higher mitotic karyorrhectic index (MKI) and MYCN amplification (chi-square test, P < 0.001), whereas neither 1p36 deletion nor 1p36 imbalance significantly correlated with a higher MKI (chi-square test, P > 0.05). We conclude that 1p36 deletion may be a reliable parameter in determining unfavorable histology and predicting prognosis in NB. Further studies with prognostic data are needed to highlight its clinical significance.