p16(INK4A)蛋白过表达及转录活性人乳头瘤病毒感染在喉鳞状细胞癌中的频率及预后意义
Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma.
作者信息
Young R J, Urban D, Angel C, Corry J, Lyons B, Vallance N, Kleid S, Iseli T A, Solomon B, Rischin D
机构信息
1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
1] Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia [2] Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
出版信息
Br J Cancer. 2015 Mar 17;112(6):1098-104. doi: 10.1038/bjc.2015.59.
BACKGROUND
Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed.
METHODS
We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes.
RESULTS
Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19-2.03, P=0.43).
CONCLUSIONS
p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.
背景
人乳头瘤病毒（HPV）感染是一部分头颈部鳞状细胞癌，特别是口咽癌中一种有力的预后生物标志物。然而，HPV在非口咽部位，如喉中的作用仍未得到证实。
方法
我们通过免疫组织化学（IHC）评估了324例喉鳞状细胞癌（LSCC）患者中p16（INK4A）（p16）蛋白的表达，并通过RNA原位杂交（ISH）评估了高危HPV E6和E7 mRNA转录本。p16表达和HPV状态与临床病理特征及预后相关。
结果
在307例可进行p16 IHC评估的患者中，20例（6.5%）为p16阳性。女性和淋巴结阳性患者更可能为p16阳性（P<0.05）。p16阳性和阴性病例之间没有其他显著的临床或人口统计学差异。p16阳性和阴性患者的总生存期（OS）没有差异，两组的2年生存率均为79%（HR=0.83，95%CI 0.36-1.89，P=0.65）。p16阳性和阴性患者的无失败生存期（FFS）没有统计学显著差异，p16阳性和阴性患者的2年FFS分别为79%和66%（HR=0.60，95%CI 0.26-1.36，P=0.22）。仅发现7例HPV RNA ISH阳性，所有这些病例均为p16 IHC阳性。HPV RNA ISH阳性肿瘤患者与阴性肿瘤患者的OS没有统计学显著差异，2年生存率分别为86%和71%（HR=0.76，95%CI 0.23-2.5，P=0.65）。2年FFS分别为86%和59%（HR=0.62，95%CI 0.19-2.03，P=0.43）。
结论
p16过表达在LSCC中不常见，高危HPV转录本病例的比例甚至更低。p16 IHC或HPV RNA ISH状态与OS或疾病预后之间没有统计学显著相关性。
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