Rb and p16INK4a expression in resected non-small cell lung tumors.
Rb and p16INK4a expression in resected non-small cell lung tumors.
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发表时间：
1996-08
期刊：
影响因子：
11.2
通讯作者：
R. Kratzke;T. M. Greatens;J. Rubins;M. Maddaus;D. Niewoehner;G. Niehans;J. Geradts
中科院分区：
文献类型：
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作者：
R. Kratzke;T. M. Greatens;J. Rubins;M. Maddaus;D. Niewoehner;G. Niehans;J. Geradts
细胞周期蛋白依赖性激酶抑制剂p16 INK 4a（CDKN 2/MTS 1）的失活在多种癌细胞系和肿瘤中均有记载。我们已经表明，p16 INK 4a蛋白表达的丧失是早期非小细胞肺癌（NSCLC）中的常见事件，与显著较差的生存率相关，并且在更高阶段的疾病中更常见。在同一个机构，对100例接受明确开胸手术的NSCLC肿瘤患者的p16 INK 4a和视网膜母细胞瘤蛋白（pRB）表达进行了检测。在15%的肿瘤中发现了异常的pRB染色，而51%的肿瘤具有异常的p16 INK 4a蛋白表达。免疫组化检测p16 INK 4a异常表达的肿瘤患者生存率显著降低（P=0.04）。此外，先前在肺癌细胞系和肿瘤中观察到的pRB和p16 INK 4a表达的负相关性在这个大的患者队列中得到证实，65%的肿瘤显示pRB和p16 INK 4a的负表达（p=0.00019）。p16 INK 4a异常表达及p16 INK 4a和pRB的反向表达随疾病病理分期的增加而显著增加。这些发现确立了切除的NSCLC中p16 INK 4缺失的预后意义，并证实了在NSCLC的分子肿瘤发生和进展中破坏细胞周期蛋白依赖性激酶介导的pRB磷酸化途径的至关重要性。
Inactivation of the cyclin-dependent kinase inhibitor p16INK4a (CDKN2/MTS1) is documented in a wide variety of cancer cell lines and tumors. We have shown that loss of p16INK4a protein expression is a common event in early stage non-small cell lung cancer (NSCLC), correlates with a significantly worse survival, and is more common in higher stage disease. One hundred NSCLC tumors from patients undergoing definitive thoracotomies at a single institution were examined for p16INK4a and retinoblastoma protein (pRB) expression. Abnormal pRB staining was identified in 15% of the tumors, whereas 51% possessed aberrant p16INK4a protein expression. Tumors with aberrant expression of p16INK4a by immunohistochemistry were associated with a significantly worse survival (P=0.04). Additionally, the inverse correlation of pRB and p16INK4a expression previously noted in lung cancer cell lines and tumors was confirmed in this large cohort of patients, with 65% of the tumors demonstrating inverse expression of pRB and p16INK4a (p=0.00019). A statistically significant increase in aberrant p16INK4a expression, as well as inverse expression of p16INK4a and pRB, was seen with increasing pathological stage of disease. These findings establish the prognostic significance (of the absence of p16INK4, in resected NSCLC and confirm the critical importance of disrupting the pathway of cyclin-dependent kinase-mediated phosphorylation of pRB in the molecular oncogenesis and progression of NSCLC.