With MYCN Amplification and trkA Expression

There is a reproducible correlation between the molecular event of MYCN amplification and the morphological manifestations in pNTs (Shimada et al. 1995; Goto et al. 2001). Those tumors with amplified MYCN typically are of the undifferentiated or poorly differentiated subtype of neuroblastoma (Schwann-ian stroma-poor) with markedly increased mitotic (proliferating) and karyorrhectic (apoptotic) activities (Shimada et al. 1995; Goto et al. 2001), an unfavorable histology group according to the International Neuroblastoma Pathology Classification. The presence of prominent nucleoli in neuroblastic cells of undifferentiated or poorly differentiated neuroblas-toma, often associated with unfavorable prognosis (Ambros et al. 2002), can be an additional hallmark of MYCN amplification (own unpublished observations).

The balance appears to favor cellular proliferation (mitosis) more than cellular death (karyorrhexis) in a MYCN amplified tumor, which is well known to have a highly aggressive and rapidly progressive clinical behavior. In light microscopic sections from MYCN amplified tumors, however, the number of karyorrhectic cells always exceeds that of mitotic cells. This may be explained by the fact that the histologically visible stage of mitosis is much shorter than that of karyorrhexis (Bursch at al. 1991). Our preliminary data show that neuroblastoma tumors with favorable histology express significantly higher levels of trkA than those with unfavorable histology (Shimada et al. 2004). Favorable histology neuroblastoma tumors include both poorly differentiated and differentiating subtypes: although there is no difference in the level of trkA expression between these two histo-logical subtypes, tumors of differentiating subtype are diagnosed in significantly older children (usually between 1 and 5 years of age) than those of poorly differentiated subtype (newborn to 1.5 years of age). This may suggest an in vivo latent period required for morphological evidence of neuroblastic differentiation among the neuroblastoma tumors in the favorable-histology group, and supports the concept of an age-linked Pathology Classification.

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