Alterations of cell cycle regulators are less frequent in advanced non-small cell lung cancer than in resectable tumours.
Alterations of cell cycle regulators are less frequent in advanced non-small cell lung cancer than in resectable tumours.
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与可切除肿瘤相比，晚期非小细胞肺癌中细胞周期调节因子的改变频率较低。
DOI：
10.1016/s0169-5002(01)00196-9
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发表时间：
2001
期刊：
影响因子：
5.3
通讯作者：
D. Betticher
中科院分区：
文献类型：
--
作者：
M. Gugger;A. Kappeler;S. Vonlanthen;H. Altermatt;H. Ris;D. Lardinois;M. Borner;J. Heighway;D. Betticher
肺癌的预后与诊断时所处的疾病阶段有关。在这项研究中，我们研究了在诊断时处于不同阶段的一系列NSCLC （n=92）中控制细胞周期的途径的改变，特别是pRb-cyclinD1-p16α和p53-p14ARF。免疫组化检测视网膜母细胞瘤蛋白（pRb）、细胞周期蛋白D1、p16α、p53和p14ARF的表达。I-IIIA期肿瘤（可切除）比晚期肿瘤（IIIB-IV期）更容易发生pRb-cyclinD1-p16α通路的改变（90%对63%，P=0.002）。pRb和p14ARF在可切除肿瘤中下调频率更高（P≤0.03），cyclin D1、p16α和p53在可切除肿瘤和晚期肿瘤中发生相似频率的改变。在12例患者中，转移部位（5例淋巴结，3例骨转移，2例脑转移和2例胃肠道转移）可与原发肿瘤进行比较：19例蛋白表达改变与原发肿瘤一致，6例（4例）仅在转移灶中发现，特别是在淋巴结转移（3例）。与正常蛋白表达相比，两种途径的改变均与更长的生存期相关（P=0.02）。在多变量分析（Cox回归）中，在调整了年龄、分期和肿瘤分化后，这种差异没有得到维持。Cyclin D1是可切除肿瘤中唯一具有独立预后价值的蛋白：未Cyclin D1过表达的肿瘤局部复发的相对风险为4.7 （P=0.02， Cox回归分析）。没有研究的蛋白质对不可切除肿瘤化疗后的反应具有预测意义。这些结果表明阶段和通路改变之间存在很强的相关性，细胞周期调节因子在晚期NSCLC中不太可能改变。因此，在这些控制通路中存在缺陷的肿瘤倾向于保持局部，并在肿瘤发展的后期阶段转移。这一发现可能解释了可切除与晚期疾病的不同生物学行为（如化疗反应）。
Prognosis of lung cancer is related to stage of disease at time of diagnosis. In this study we examine alterations of pathways governing the cell cycle, in particular pRb-cyclinD1-p16α and p53-p14ARF, in a series of NSCLC (n=92) at different stages at diagnosis. Using immunohistochemistry, we assessed the expression of the retinoblastoma protein (pRb), cyclin D1, p16α, p53 and p14ARF. Tumours in stage I-IIIA (resectable) were more likely to have alterations in the pRb-cyclinD1-p16α pathway than tumours in advanced stage (IIIB–IV) (90% versus 63%, P=0.002). pRb and p14ARF were more frequently downregulated in resectable tumours (P≤0.03), and cyclin D1, p16α, and p53 were altered at a similar frequency in resectable and advanced tumours. In 12 patients, metastatic sites (5 lymph node, 3 bone, 2 brain and 2 gastrointestinal metastases) were available for comparison with the primary tumour: 19 altered protein expressions were found to be concordant, six additional alterations (in 4 patients) were found in the metastases only, especially in lymph node metastases (3 patients). Compared with normal protein expression, both pathway alterations were associated with a longer survival (P=0.02). In a multivariate analysis (Cox regression) this difference was not maintained after adjustment for age, stage and tumour differentiation. Cyclin D1 was the sole protein with independent prognostic value in resectable tumours: the relative risk of local relapse was 4.7 in tumours without cyclin D1 overexpression (P=0.02, Cox regression analysis). No protein studied had a predictive significance for response after chemotherapy in non-resectable tumours. These results demonstrate a strong correlation between stage and pathway alterations, cell cycle regulators being less likely altered in advanced NSCLC. Tumours with defects in these control pathways tend therefore to remain localised and to metastasise at a later phase in tumour development. This finding might be an explanation for distinct biological behaviour (e.g. chemotherapy response) of resectable versus advanced disease.
DOI：
--
发表时间：
1972
期刊：
--
影响因子：
--
作者：
D. Cox
通讯作者：
D. Cox
影响因子：
11.2
作者：
Geoffrey I. Shapiro;Christian D. Edwards;Lester Kobzik;J. Godleski;William G. Richards;D. Sugarbaker;B. Rollins
通讯作者：
Geoffrey I. Shapiro;Christian D. Edwards;Lester Kobzik;J. Godleski;William G. Richards;D. Sugarbaker;B. Rollins
影响因子：
15.9
作者：
Kornmann, M;Arber, N;Korc, M
通讯作者：
Korc, M