Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas
Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas
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DOI：
10.1007/s00428-008-0689-3
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发表时间：
2008-12-01
期刊：
影响因子：
3.5
通讯作者：
Popper, Helmut
中科院分区：
文献类型：
--
作者：
Dacic, Sanja;Kothmaier, Hannelore;Popper, Helmut
p16/CDKN2A纯合子缺失是恶性间皮瘤中最常见的遗传异常。本研究的目的是通过免疫组织化学和荧光原位杂交（FISH）确定p16/CDKN2A缺失在恶性胸膜间皮瘤（MPM）中的预后意义。高密度组织微阵列是由48个MPM的档案标本用福尔马林固定石蜡包埋而成。长生存期（LS）定义为自诊断时起超过3年的生存期，短生存期定义为自诊断时起不到3年的生存期。免疫组化检测p16蛋白表达缺失和FISH检测p16纯合子缺失均与不良预后相关。女性、p16阳性免疫表达和缺乏p16/CDKN2A缺失显著预测LS组的生存。统计分析显示免疫组织化学和FISH数据有很强的相关性。p16免疫表达阳性、9p21缺失阴性的患者存活时间最长。我们的研究首次证明，与快速致死的间皮瘤患者相比，长期生存期大于3年的胸膜间皮瘤患者中9p21纯合缺失和p16免疫反应性丧失的频率降低。应考虑将这些试验应用于MPM的术前预测和治疗决策。
Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.