MYCN protein expression as a predictor of neuroblastoma prognosis.
MYCN protein expression as a predictor of neuroblastoma prognosis.
复制标题
DOI：
--
复制
发表时间：
1997-10
期刊：
影响因子：
--
通讯作者：
H. Chan;B. Gallie;G. Deboer;G. Haddad;N. Ikegaki;J. Dimitroulakos;H. Yeger;V. Ling
中科院分区：
文献类型：
--
作者：
H. Chan;B. Gallie;G. Deboer;G. Haddad;N. Ikegaki;J. Dimitroulakos;H. Yeger;V. Ling
大约一半的非局部神经母细胞瘤有MYCN基因扩增，通常进展迅速，但没有这种扩增的一半也很差，尽管进展较慢。我们假设MYCN蛋白的过表达可以在没有基因扩增的情况下发生，并且这种表达可靠地预测神经母细胞瘤的预后。为了确定MYCN表达是否与预后相关，我们在180个档案前治疗和治疗后样本中检测了MYCN蛋白免疫组织化学，并根据这些常规预后因素对57例常规治疗的IVS、III和IV期患者进行了分层：分期、年龄、血清铁蛋白、岛田组织学、尿儿茶酚胺比例和MYCN基因状态。在中位随访bb0 /=6.8年时，我们发现在已知MYCN基因状态的患者中，37例无基因扩增的患者中有23例的预后并不比37例有基因扩增的患者中的14例好（P = 0.35和0.21，比较无复发率和生存率）。相反，在未检测到MYCN基因扩增的患者中，23例患者中有9例MYCN蛋白预处理过表达，比未检测到MYCN蛋白的23例患者中的14例表现更差（P = 0.0016和0.022，比较无复发率和生存率）。此外，MYCN蛋白表达对预后无影响（P = 0.00001），并根据MYCN基因状态、每个常规预后因素（P范围为0.00001-0.013）或同时根据两个最重要的因素，分期和年龄（P = 0.00076）对所有57例患者进行分层（P = 0.0007）。我们得出结论，无基因扩增的MYCN蛋白过表达与神经母细胞瘤的临床行为显著相关，并独立于其他预后因素预测预后。这有力地支持了MYCN癌基因的表达对神经母细胞瘤的进展至关重要的假设。
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.