肿瘤神经旁浸润的研究进展

Research Progression of Perineural Invasion of Tumor

目的为进一步了解肿瘤神经旁浸润(PNI)的概念、可能分子机制及临床意义,以寻找新的肿瘤治疗途径。方法对有关PNI的定义、分子机制及临床研究文献进行综述并分析。结果目前对于PNI被广泛接受的定义是肿瘤接近并包绕至少33%神经周径或者穿透三层神经鞘中的任意一层。PNI不仅仅是简单的扩散,更像是浸润和侵犯。目前主要有"低阻力通道"和"信号交互传递"两种学说用以解释其发生机制。近期的研究表明"信号交互传递"更能合理解释PNI的发生机制。而包括成纤维细胞在内的基质成分,在促进PNI发生的复杂信号通路中起着关键作用;神经营养素和轴突导向分子在PNI的进程中起调节作用。临床研究发现,PNI在头颈部肿瘤、胃癌、胰腺癌、结直肠癌、前列腺癌等恶性肿瘤中是判断预后的指标,阳性提示预后较差,5年存活率较低。结论PNI的发生机理极为复杂,关于其详细的机理仍无明确的定论,故继续这方面的研究将为揭开肿瘤PNI的机理提供理论基础,也可为肿瘤的治疗提供新的靶点。

Objective To further comprehend the definition,molecular mechanism,and clinical significance of perineural invasion（PNI） so as to explore new therapy for the tumors.Methods The literatures about the definition,molecular mechanism,and clinical study of PNI were reviewed and analyzed.Results At present,widely accepted definition of PNI was that at least 33% of the circumference of the nerve should be surrounded by tumor cells or tumor cells within any of three layers of the nerve sheath.The newest theory on molecular mechanism of PNI was that PNI was more like infiltration,invasion,not just diffusion.＂Path of low-resistance＂ and ＂Reciprocal signaling interactions＂ were the main theories.More recently,the studies had demonstrated that ＂Reciprocal signaling interactions＂ could more clearly explain the mechanism of PNI.Stromal elements,including fibroblasts,seemed to play a key role in the complex signaling interactions driving PNI.Neurotrophins and axonal guidance molecules had been implicated in promoting the progress of PNI.PNI was a prognosis index in the cancers of the head and neck,stomach,pancreas,colon and rectum,and prostate,which was positive indicated that the patients would have a poor prognosis and a low 5-year survival rate.Conclusions The mechanism of PNI is very complex,and its clear mechanism is still undefined.Keeping on researching the mechanism of PNI could provide theoretical foundation to disclose the mechanism and the therapy of PNI.