口咽鳞状细胞癌局部区域和远处转移的分子预测因子。
Molecular predictors of locoregional and distant metastases in oropharyngeal squamous cell carcinoma.
出版信息
J Otolaryngol Head Neck Surg. 2013 Oct 16;42(1):53. doi: 10.1186/1916-0216-42-53.
BACKGROUND
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing due to fundamental changes in oncogenesis related to effects of the human papilomavirus (HPV). Virally-mediated tumours behave and respond to treatment differently than their classic, carcinogenically-mediated counterparts despite similar stage and grade of disease. This difference in behaviour has lead to investigation of etiologies of OPSCC at the molecular level.
OBJECTIVE
This study was designed to identify biomarker profiles predictive of locoregional and distant metastases and recurrence in OPSCC.
METHODS
Cross-sectional study of a prospectively-collected oropharyngeal tumour database was undertaken. All patients with OPSCC presenting to the University of Alberta Hospital from 2002-2009 were included in the study. Data collection from the Alberta Cancer Registry, including demographics, nodal status, distant metastases, treatment, recurrence, and survival, was undertaken. Tissue micro-arrays (TMAs) were constructed for each tumour specimen using triplicate cores (0.6mm) of formalin-fixed, paraffin-embedded (FFPE) pre-treatment tumour tissue. TMAs were processed using immunohistochemistry for p16, EGFR, Ki67, p53, and Bcl-XL. Positivity for each biomarker was determined using quantified AQUAnalysis ® scores on histoplots. Multivariate statistics were utilized to assess the relationship between each biomarker and locoregional and distant metastases, as well as recurrence-free survival (RFS).
RESULTS
High expression of p16 (p=0.000) and Bcl-XL (p=0.039) independently demonstrated a significant association with nodal disease at presentation. Kaplan-Meier analysis demonstrated improved RFS in patients with high p16 and decreased RFS in patients with high p53 expression. Cox regression analysis supported p16 as an independent prognosticator for improved RFS. p53 demonstrated an association with recurrence, but when compared to p16 status, nodal status, and staging, was not an independent predictor of recurrence.
CONCLUSIONS
Biomarker profiling using p16, Bcl-xL, and p53 may be useful in prognostication and treatment planning in patients with OPSCC.
背景
由于与人类乳头瘤病毒（HPV）相关的致癌作用的根本变化，口咽鳞状细胞癌（OPSCC）的发病率正在增加。病毒介导的肿瘤与经典的致癌介导肿瘤相比，其行为和对治疗的反应不同，尽管疾病的阶段和分级相似。这种行为上的差异导致了对口咽鳞状细胞癌的分子水平病因的研究。
目的
本研究旨在确定预测 OPSCC 局部和远处转移及复发的生物标志物谱。
方法
对前瞻性收集的口咽肿瘤数据库进行了横断面研究。纳入 2002-2009 年期间到阿尔伯塔大学医院就诊的所有 OPSCC 患者。从艾伯塔癌症登记处收集数据，包括人口统计学、淋巴结状态、远处转移、治疗、复发和生存情况。使用福尔马林固定、石蜡包埋（FFPE）预处理肿瘤组织的三重复制核心（0.6mm）构建每个肿瘤标本的组织微阵列（TMA）。使用免疫组织化学对 p16、EGFR、Ki67、p53 和 Bcl-XL 进行处理。使用 histoplots 上的量化 AQUAnalysis ® 评分确定每个生物标志物的阳性率。利用多变量统计学评估每个生物标志物与局部和远处转移以及无复发生存率（RFS）之间的关系。
结果
p16（p=0.000）和 Bcl-XL（p=0.039）的高表达独立显示与初诊时的淋巴结疾病有显著关联。Kaplan-Meier 分析表明，p16 高表达的患者 RFS 改善，而 p53 高表达的患者 RFS 降低。Cox 回归分析支持 p16 是 RFS 改善的独立预后因素。p53 与复发有关，但与 p16 状态、淋巴结状态和分期相比，不是复发的独立预测因子。
结论
使用 p16、Bcl-xL 和 p53 的生物标志物谱分析可能有助于 OPSCC 患者的预后和治疗计划。
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