Expression Patterns of Bmi-1 and p16 Significantly Correlate With Overall, Disease-Specific, and Recurrence-Free Survival in Oropharyngeal Squamous Cell Carcinoma
Expression Patterns of Bmi-1 and p16 Significantly Correlate With Overall, Disease-Specific, and Recurrence-Free Survival in Oropharyngeal Squamous Cell Carcinoma
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DOI：
10.1002/cncr.26100
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发表时间：
2011-10-15
期刊：
影响因子：
6.2
通讯作者：
Hegyi, Ivan
中科院分区：
文献类型：
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作者：
Huber, Gerhard F.;Albinger-Hegyi, Andrea;Hegyi, Ivan
背景技术背景：本研究的目的是在252例口腔和口咽鳞状细胞癌（OSCC）患者队列中将B细胞特异性莫洛尼鼠白血病病毒整合位点1（Bmi-1）和p16的表达模式与患者结局（复发和生存）联系起来。方法：应用组织芯片技术检测252例口腔鳞癌组织中Bmi-1和p16的表达水平。通过计算强度反应性评分（IRS）确定染色强度。染色强度和肿瘤细胞内的表达定位（细胞核或细胞质）与总体、疾病特异性和无复发生存率相关。结果：大多数癌位于口咽部（61.1%）。在单因素分析中，与Bmi-1低、中度表达的患者相比，Bmi-1强表达（IRS >10）的OSCC患者预后较差（P = 0.008;风险比[HR]，1.82; 95%置信区间[CI]，1.167-2.838）;在非典型胞质Bmi-1表达中也观察到这种相关性（P = 0.001; HR，2.164; 95%CI，1.389-3.371）和阴性p16表达（P <0.001; HR，0.292; 95%CI，0.178-0.477）。正如预期的那样，两种标志物的组合与总生存率有更强的相关性（P <0.001; HR，8.485; 95%CI，4.237-16.994）。多变量分析表明口咽癌患者的结果显著，但口腔肿瘤患者的结果不显著：肿瘤分类（P = 0.011; HR，1.838; 95%CI，1.146-2.947）和联合标志物表达模式（P <0.001; HR，6.254; 95%CI，2.869-13.635）与总生存期、疾病特异性生存期相关。（肿瘤分类：P = 0.002; HR，2.807; 95% CI，1.477-5.334;联合标志物：P = 0.002; HR，5.386;联合标志物也与无复发生存率相关（P = 0.001; HR，8.943; 95%CI，2.562-31.220）。结论：胞浆Bmi-1表达，p16表达缺失，特别是这2种预测标志物的组合与口咽癌患者的疾病特异性和无复发生存率呈负相关。因此，目前的结果表明，这些可能适用于作为预测标志物与其他因素相结合，以选择患者进行更积极的治疗和随访。Cancer 2011;117：4659-70. (C)2011年美国癌症协会
BACKGROUND: The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC). METHODS: Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival. RESULTS: The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P = .001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95% CI, 1.146-2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P = .001; HR, 8.943; 95% CI, 2.562-31.220). CONCLUSIONS: Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up. Cancer 2011;117:4659-70. (C) 2011 American Cancer Society.