MYCN protein expression as a predictor of neuroblastoma prognosis
| Autor: | H S, Chan, B L, Gallie, G, DeBoer, G, Haddad, N, Ikegaki, J, Dimitroulakos, H, Yeger, V, Ling |
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| Rok vydání: | 1998 |
| Předmět: |
Ontario
Adolescent Gene Amplification Genes myc Infant Combined Modality Therapy Survival Analysis Disease-Free Survival Neoplasm Proteins Cohort Studies Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-myc Neuroblastoma Treatment Outcome Risk Factors Child Preschool Biomarkers Tumor Disease Progression Humans Life Tables Child Neoplasm Staging Retrospective Studies |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 3(10) |
| ISSN: | 1078-0432 |
| Popis: | 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 overexpression 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 assayed MYCN protein immunohistochemically in 180 archival pretreatment and posttreatment samples and stratified the 57 conventionally treated stage IVS, III, and IV patients by these conventional prognostic factors: stage, age, serum ferritin, Shimada histology, urinary catecholamine ratio, and MYCN gene status. At a median follow-up of/=6.8 years, we found in patients with known MYCN gene status that the 23 of 37 without gene amplification fared no better than the 14 of 37 with gene amplification (P = 0.35 and 0.21, comparing relapse-free and survival rates). Conversely, in patients without MYCN gene amplification, 9 of 23 were found to overexpress MYCN protein pretreatment, and they did worse than the 14 of 23 without detectable MYCN protein (P = 0.0016 and 0.022, comparing relapse-free and survival rates). Furthermore, MYCN protein expression was prognostic without (P = 0.00001) and with (P = 0.0007) stratifying all 57 patients by MYCN gene status, each conventional prognostic factor (P ranging from 0.00001-0.013), or simultaneously by the two most important factors, stage and age (P = 0.00076). We conclude that overexpression of MYCN protein without gene amplification correlated significantly with the clinical behavior of neuroblastoma and predicted outcome independently of other prognostic factors. This strongly supports the hypothesis that expression of the MYCN oncogene is critical for progression of neuroblastoma. |
| Databáze: | OpenAIRE |
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