MYCN PROTEIN EXPRESSION AS A PREDICTOR OF NEUROBLASTOMA PROGNOSIS

About half of nonlocalized neuroblastomas have MYCN gene amplification and usually progress rapidly, but the half without such amplification also do poorly, albeit progressing more slowly, We hypothesize that o verexpression of MYCN protein can occur without gene amplification and that this expression reliably predicts the prognosis of neuroblastoma , To determine whether MYCN expression correlated with outcome, we ass ayed MYCN protein immunohistochemically in 180 archival pretreatment a nd posttreatment samples and stratified the 57 conventionally treated stage IVS, III, and IV patients by these conventional prognostic facto rs: stage, age, serum ferritin, Shimada histology, urinary catecholami ne ratio, and MYCN gene status, At a median follow-up of greater than or equal to 6.8 Sears, we found in patients,vith known MYCN gene statu s that the 23 of 37 without gene amplification fared no better than th e 14 of 37 with gene amplification (P = 0.35 and 0.21, comparing relap se-free and survival rates), Conversely, in patients without MYCN gene amplification, 9 of 23 were found to overexpress MYCN protein pretrea tment, and they did worse than the 14 of 23 without detectable MYCN pr otein (P = 0.0016 and 0.022 comparing relapse-free and survival rates) , Furthermore, MYCN protein expression was prognostic without (P = 0.0 0001) and with (P = 0.0007) stratifying all 57 patients by MYCN gene s tatus, each conventional prognostic factor (P ranging from 0.00001-0.0 13), or simultaneously by the two most important factors, stage and ag e (P = 0.00076), We conclude that overexpression of MYCN protein witho ut gene amplification correlated significantly with the clinical behav ior of neuroblastoma and predicted outcome independently of other prog nostic factors. This strongly supports the hypothesis that expression of the MYCN oncogene is critical for progression of neuroblastoma.