p16INK4A genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas
p16INK4A genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas
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DOI：
10.1016/j.humpath.2007.08.004
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发表时间：
2008-03-01
期刊：
影响因子：
3.3
通讯作者：
O'Leary, John J.
中科院分区：
文献类型：
--
作者：
O'Regan, Esther M.;Toner, Mary E.;O'Leary, John J.
头颈部鳞状细胞癌（HNSCC）通常影响55岁以上的男性吸烟者。最近，已认识到年轻人中HNSCC的发病率增加，其中许多是非吸烟者和女性。已知p16的功能失活是HNSCC中的常见事件，主要通过缺失或甲基化。该小组先前的一项研究表明，HNSCC中p16缺失与年龄显著相关。本研究的主要目的是评估HNSCC中p16的其他分子改变，特别是与年龄、部位和人乳头瘤病毒（HPV）状态的关系。前瞻性确定了年龄范围为22至76岁的HNSCC患者（n = 24）。甲基化特异性聚合酶链反应和免疫组化分别用于评估p16基因失活和p16蛋白表达。HPV 16状态确定每个病例。总体而言，p16失活是一个常见的事件中检测到46%的情况下。p16甲基化在女性比男性更常见（P = .05）。所有p16甲基化的病例均来自舌前区，其中75%为年轻患者。结果表明，p16甲基化在40岁以下的人中更常见，而p16缺失在40岁以上的人中更常见。因此，似乎HNSCC中p16失活的特定模式与特定患者的风险特征相关。有趣的是，HPV 16信使RNA仅在HNSCC中从舌根病变中检测到，并且仅在男性中发现。这与年轻人中HNSCC的患者特征不同，后者影响前舌和通常的女性，因此，这种病毒极不可能是这些年轻人中HNSCC的主要病原体。(c)2008年爱思唯尔公司All rights reserved.
Head and neck squamous cell carcinoma (HNSCC) typically affects male smokers older than 55 years. Recently, an increase in the incidence of HNSCC in young adults has been recognized, many of them nonsmokers and females. Functional inactivation of p16 is known to be a common event in HNSCC, mainly by either deletion or methylation. A previous study by this group has shown that p16 deletions in HNSCC are significantly associated with age. The primary objective of this study was to evaluate additional molecular alterations of p16 in HNSCC, specifically in relation to age, site, and human papillomavirus (HPV) status. Patients ranging in age from 22 to 76 years with HNSCC were prospectively identified (n = 24). Methylation-specific polymerase chain reaction and immunohistochemistry were used to evaluate p16 gene inactivation and p16 protein expression, respectively. HPV 16 status was determined for each case. Overall, p16 inactivation was a frequent event detected in 46% of cases. Methylation of p16 was more often detected in females than males (P = .05). All cases showing p16 methylation were from the anterior tongue, and 75% of them were young patients. The results indicate that p16 methylation is a more common event in those younger than 40 years in contrast to p16 deletions, which are more common in those older than 40 years. Consequently, it appears that specific modes of inactivation of p16 in HNSCC are related to specific patient risk profiles. Interestingly, HPV 16 messenger RNA was detected exclusively in HNSCC from the base of tongue lesions and was only found in males. This differs from the patient profile of HNSCC in the young, which affects the anterior tongue and commonly females, thus, making it highly unlikely that this virus is a primary causative agent of HNSCC in these young adults. (c) 2008 Elsevier Inc. All rights reserved.