Frequent p16 inactivation by homozygous deletion or methylation is associated with a poor prognosis in Japanese patients with pleural mesothelioma
Frequent p16 inactivation by homozygous deletion or methylation is associated with a poor prognosis in Japanese patients with pleural mesothelioma
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DOI：
10.1016/j.lungcan.2008.02.013
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发表时间：
2008-10-01
期刊：
影响因子：
5.3
通讯作者：
Date, Hiroshi
中科院分区：
文献类型：
--
作者：
Kobayashi, Naruyuki;Toyooka, Shinichi;Date, Hiroshi
本研究检测了日本恶性胸膜间皮瘤(MPM)标本中p16基因的表达状态和p16基因的缺失和甲基化状态。对30例日本原发MPM标本进行P16蛋白免疫组织化学染色和P16基因荧光原位杂交。采用甲基化特异性聚合酶链式反应检测了13例患者的P16基因甲基化状态，这些患者的冰冻肿瘤标本是可用的。在30例患者中，有24例(80.0%)p16蛋白表达丢失。21例患者存在纯合子缺失，9例患者保留了P16基因。P16纯合子缺失患者中无一例p16阳性表达，3例保留P16基因的患者未见p16阳性表达。两名P16基因完整但无p16表达的患者存在异常的P16甲基化。这些结果表明P16基因的纯合缺失或甲基化是导致P16失活的原因。在预后方面，p16表达阴性的患者生存期明显缩短。与p16阳性表达组比较，差异有统计学意义(P=0.040)。我们的研究表明，由纯合子缺失或甲基化导致的P16失活在日本MPMS患者中是一种常见事件，与预后不良有关。纯合缺失是P16失活的主要原因，但当保留P16等位基因时，甲基化也会导致P16失活。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
This study examined the p16 expression status and the P16 gene deletion and methylation status in specimens from Japanese patients with malignant pleural mesothelioma (MPM). lmmunohistochemical staining for p16 protein and fluorescence in situ hybridization for the P16 gene were performed using specimens from 30 Japanese patients with primary MPM. The methylation status of the P16 gene was examined in 13 patients whose frozen tumor specimens were available using a methylation-specific PCR assay. Among the 30 patients, the toss of p16 protein expression was observed in 24 patients (80.0%). Twenty-one patients had homozygous deletions, and 9 patients retained the P16 gene. None of the patients with P16 homozygous deletions exhibited p16-positive expression, and 3 patients who retained the P16 gene did not exhibit p16-positive expression. Aberrant P16 methylation was present in two patients with an intact P16 gene but without p16 expression. These results suggest that either a homozygous deletion or methylation is responsible for P16 inactivation. Regarding the prognosis, patients with p16-negative expression had a significantly shorter survival. time than those with p16-positive expression (P=0.040). Our study showed that P16 inactivation by homozygous deletions or methylation is a frequent event in Japanese patients with MPMs, relating to poor prognosis. Homozygous deletion is the major cause of P16 inactivation, but methylation also lead to the inactivation of P16 when the P16 alleles are retained. (C) 2008 Elsevier Ireland Ltd. All rights reserved.