ID2 expression in neuroblastoma does not correlate to MYCN levels and lacks prognostic value

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Abstract
The MYCN proto-oncogene is frequently amplified in a subgroup of highly aggressive neuroblastomas. The molecular mechanism(s) by which the overexpressed MYCN contributes to an aggressive tumor cell behavior is not well understood. Recently, it was reported that the ID2 gene is a direct target for the MYCN and MYC transcription factors, and that ID2 expression and MYCN amplification correlate positively in neuroblastoma. In addition, ID2 expression was proposed as a negative prognostic parameter. As these results are of potential clinical importance, but not in agreement with our own initial observations, the putative correlation between ID2 and MYC(N) expression in neuroblastoma cell lines and tumors was reinvestigated. We found no correlation between MYCN and ID2 expression in neuroblastoma cell lines or tumor specimens. However, we did find a significant positive correlation between MYC and ID2 expressions in both MYCN-amplified and single-copy tumor specimens, and in MYCN single-copy cell lines. As previously reported, we also found an inverse correlation between MYC and MYCN expressions. Importantly, we could not confirm the reported prognostic power of ID2-expression in neuroblastoma. These data, obtained in two independent laboratories, challenge the previously proposed ID2–MYCN relation.