Akervall Jan
Department of Otolaryngology, Head and Neck Surgery, University Hospital, Sweden.
Cancer Metastasis Rev. 2005 Jan;24(1):87-94. doi: 10.1007/s10555-005-5049-z.
Survival for patients with squamous cell carcinoma of the head and neck (SCCHN) is still poor, despite great technical improvements in radiotherapy and surgery. A possible explanation for this is the lack of individualization in treatment based on biological properties of the tumors, resulting in over- as well as under treatment. Management of SCCHN has mainly been based on TNM classification over the last decades. However, a large amount of studies have shown that biomarkers may add prognostic information, independently of the TNM system, indicating that biological aggressiveness is not entirely reflected by the T- and N-status of the tumor. A conclusion to draw from this is that the present standardized treatment based on macroscopic features of the tumor in many cases will result in suboptimal treatment since important underlaying genetic properties of the tumors are not taken into consideration. A variety of laboratory techniques have been used in studies that investigate the individual biological features, spanning from methods that screen the genome for chromosomal and genetic abnormalities, e.g. cytogenetics, CGH, SKY, cDNA micro array to detailed studies of specific aberrations, e.g. southern, northern and western blotting, PCR based analysis and immunohistochemistry. Dysregulation of genes involved in e.g. cell cycle control, proliferation, drug resistance, and metastasis have been linked to outcome of treatment and survival. The purpose of this review of the literature was to summarize what has been studied so far by cDNA micro array techniques with regards to genetic screening in general and biomarkers that relate to response to therapy and prediction of clinical outcome in particular. We conclude that the majority of investigations that focus on gene profiling have a descriptive character, e.g. comparisons of tumor and normal cells, metastatic and non-metastatic properties, and differences between sub-sites and grades of differentiation. There are just a handful studies that so far have investigated how gene profiling can be used to predict clinical course.
尽管放射治疗和手术技术有了很大改进,但头颈部鳞状细胞癌(SCCHN)患者的生存率仍然很低。对此的一个可能解释是,基于肿瘤生物学特性的治疗缺乏个体化,导致治疗过度和不足。在过去几十年中,SCCHN的治疗主要基于TNM分类。然而,大量研究表明,生物标志物可能会提供独立于TNM系统的预后信息,这表明肿瘤的生物学侵袭性并不完全由肿瘤的T和N状态反映。由此得出的结论是,目前基于肿瘤宏观特征的标准化治疗在许多情况下会导致治疗效果欠佳,因为肿瘤重要的潜在遗传特性未被考虑在内。各种实验室技术已用于研究个体生物学特征,从筛选基因组中的染色体和基因异常的方法,如细胞遗传学、比较基因组杂交(CGH)、光谱核型分析(SKY)、cDNA微阵列,到对特定畸变的详细研究,如Southern印迹、Northern印迹和Western印迹、基于聚合酶链反应(PCR)的分析以及免疫组织化学。参与细胞周期调控、增殖、耐药性和转移等过程的基因失调与治疗结果和生存率相关。这篇文献综述的目的是总结到目前为止通过cDNA微阵列技术在遗传筛查方面,特别是与治疗反应和临床结果预测相关的生物标志物方面所进行的研究。我们得出的结论是,大多数专注于基因谱分析的研究具有描述性特征,例如肿瘤细胞与正常细胞的比较、转移与非转移特性以及不同亚部位和分化程度之间的差异。到目前为止,只有少数研究探讨了基因谱分析如何用于预测临床病程。