Clinical outcome in stage I to III breast carcinoma and eIF4E overexpression
Clinical outcome in stage I to III breast carcinoma and eIF4E overexpression
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DOI：
10.1097/00000658-199805000-00016
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发表时间：
1998-05-01
影响因子：
9
通讯作者：
De Benedetti, A
中科院分区：
文献类型：
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作者：
Li, BDL;McDonald, JC;De Benedetti, A
本研究的目的是确定高真核起始因子4E （elF4E）过表达（在良性乳腺组织中升高7倍或更多）是否与较差的临床结果相关。背景数据选择性过表达特定蛋白导致细胞功能失调可导致恶性转化。elF4E的过表达优先增加长且富含G-C的5'-非翻译区mrna的翻译。选择性基因产物，如肿瘤新血管生成因子、鸟氨酸脱羧酶和细胞周期蛋白D1，被上调。方法对114例乳腺标本进行分析，采用Western blot法定量检测elF4E过表达。采用兔抗elF4E抗体定量elF4E蛋白水平，并采用硝基蓝四氮唑和5-溴-4-氯-3-吲哚酰磷酸进行Western blots比色开发。对斑点进行扫描并进行密度分析。分析了治疗、病理和临床结果数据变量。通过统计学分析确定elF4E过表达是否与乳腺癌临床结果相关。结果55例良性标本中elF4E的平均表达量为1.1 +/- 0.4倍（平均±标准差）。所有59例恶性乳腺癌标本均发现elF4E过表达（范围为1.9 ~ 30.6倍），平均过表达10.8 +/- 6.3倍。恶性标本中elF4E的平均表达水平高于良性标本（p < 0.05，无配对t检验）。elF4E过表达的程度似乎与T和N期无关。在21例elF4E过表达低于7倍的患者中，有1例癌症复发，但无癌症相关死亡。在38例elF4E高表达（7倍以上）患者中，14例乳腺癌复发（p = 0.03，对数秩检验），其中11例死亡（p = 0.04，对数秩检验），本研究平均随访时间为40个月。结论与elF4E低过表达的同期乳腺癌患者相比，elF4E高过表达的I ~ III期乳腺癌患者的癌症复发率和癌症相关死亡率更高。因此，elF4E蛋白过表达可能对I ~ III期乳腺癌具有预后价值。
ObjectiveThe objective of this study is to determine if high eukaryotic initiation factor 4E (elF4E) overexpression (sevenfold elevation or more over benign breast tissue) is associated with a worse clinical outcome.Summary Background DataDysregulation of cellular functions by selective overexpression of specific proteins can lead to malignant transformation. The overexpression of elF4E preferentially increases translation of mRNAs with long, G-C rich 5'-untranslated regions. Selective gene products, such as tumor neoangiogenic factors, ornithine decarboxylase, and cyclin D1, are upregulated.MethodsOne hundred fourteen breast specimens were analyzed and elF4E overexpression was quantified by Western blot analysis. Quantification for elF4E protein level was accomplished using a rabbit anti-elF4E antibody and colorimetric development of Western blots using nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate. The blots were scanned and analyzed by densitometry. Treatment, pathologic, and clinical outcome data variables were analyzed. Statistical analysis was performed to determine if elF4E overexpression is associated with breast cancer clinical outcome.ResultsIn the 55 benign specimens, the mean elF4E expression was 1.1 +/- 0.4 fold (mean +/- standard deviation). All 59 malignant breast carcinoma specimens were noted to have elF4E overexpression (range, 1.9-fold to 30.6-fold), with a mean overexpression of 10.8 +/- 6.3-fold. The mean level of elF4E expression in malignant specimens was higher than benign specimens (p < 0.05, unpaired t test). The degree of elF4E overexpression appears to be independent of T and N stage.In the 21 patients with elF4E overexpression of less than sevenfold, there was one cancer recurrence but no cancer-related deaths. In the 38 patients with high elF4E overexpression (sevenfold or more), 14 patients had breast cancer recurrences (p = 0.03, log rank test), of whom 11 have died from the disease (p = 0.04, log rank test), The average follow-up interval in this study was 40 months.ConclusionsPatients with stage I to III breast cancer and high elF4E overexpression had a higher rate of cancer recurrence and a higher rate of cancer-related death when compared to similar-stage breast cancer patients with low elF4E overexpression. Therefore, elF4E protein overexpression may be of prognostic value in stage I to III breast carcinoma.