Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma
Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma
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DOI：
10.1158/1078-0432.ccr-06-1759
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发表时间：
2006-11-15
影响因子：
11.5
通讯作者：
Pilotti, Silvana
中科院分区：
文献类型：
--
作者：
Perrone, Federica;Suardi, Simona;Pilotti, Silvana
目的：本研究的目的是进一步了解头颈部鳞状细胞癌（HNSCC）的发病途径，这可能有助于识别有助于开发更特异性治疗方法的新生物标志物。在来自单一机构的一组手术治疗患者的90例口咽SCC中分析了细胞周期调节因子和表皮生长因子受体（EGFR）和BRAF基因，结果：至少有四组不同的肿瘤被鉴定为共享一个共同的组织学，但显示不同的分子/细胞遗传学模式：（a）19%是HPV阳性SCC，其缺乏所研究基因的改变可以解释其特定的自然史，这需要较低的侵袭性治疗;（B）37%是携带TP 53突变的HPV阴性SCC，其可以通过通过非p53依赖性细胞凋亡起作用的药物更有效地治疗;（c）34%为携带野生型TP 53和9 p21（p16（INK 4a）和p15（INK 4 b））缺失和/或细胞周期蛋白D1过表达的HPV阴性SCC，这证明用DNA损伤药物治疗后再用细胞周期抑制剂治疗是合理的;（d）10%为HPV阴性，缺乏肿瘤抑制基因和细胞周期改变。第二，第三和第四组也表现出增加的拷贝数的EGFR和染色体7（43%），这可能证明额外或替代使用EGFR inhibitors.Conclusions：我们的研究结果表明，评估HPV TP 53，9 p21，和EGFR状态可能是至关重要的口咽鳞状细胞癌找到更多的定制和有益的治疗。
Purpose:The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches.Experimental Design: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status.Results: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16(INK4a) and p15(INK4b)) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors.Conclusions: Our findings suggest that assessing HPV TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs.