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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma.
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Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma.

机译：临床因素和预后意义一种蛋白激酶激活患者支气管肺泡癌。

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PURPOSE: Lung cancer is the leading cause of cancer related mortality in the world. Bronchioloalveolar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. METHODS: Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. RESULTS: Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI, 1.07-4.71, p=0.032), advanced stage (III or IV) (HR 2.17, 95% CI, 1.004-4.71, p=0.049) and smoking status (HR 6.89, 95% CI, 1.49-31.88, p=0.013) were associated with a worse prognosis. CONCLUSIONS: Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.
机译：目的:肺癌的主要原因世界上癌症相关的死亡率。支气管肺泡癌(BAC)的一个子集非小细胞肺癌,最近因为引起了人们的关注不同的生物和临床特征,发病率增加,和增强的响应能力新疗法,如表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)。然而,BAC预后功能没有是定义良好的。高度流行的和一个贫穷的预后因素其他类型的非小细胞肺癌,我们评估预后临床特征和Akt的重要性激活BAC患者。46例BAC在冰岛机密根据世卫组织1999年的标准。评估使用两个phospho-specific吗一种蛋白激酶抗体(S473和T308)免疫组织化学(包含IHC)分析。和其他两个命令之间的一种蛋白激酶水平使用一个精确的参数进行了评估Cochran-Armitage测试的趋势。分析了kaplan meier和log-rank方法测试,风险比率(人力资源)由考克斯比例风险模型。也用于评估多个的联合效应因素对生存时,他们被认为是同时进行。(粘液和non-mucinous)与生存相关。在BAC非常普遍,只有2 46患者表现出负染法抗体63%的病例中观察到,联系在一起non-mucinous组织学。与生存或差异有关吸烟状况。显示,男性性别(HR 2.24, 95%可信区间,1.07 - -4.71, p = 0.032),晚期(III或IV)(HR 2.17, 95% CI, 1.004 - -4.71, p = 0.049)吸烟状态(HR 6.89, 95% CI, 1.49 - -31.88,p = 0.013)与预后差相关。结论:男性,高级阶段,尤其是吸烟状态(但不是一种蛋白激酶激活)是潜在的重要的预后BAC的特性。认为在设计和解释招收BAC病人的临床试验。

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