Redefining Perineural Invasion: Integration of Biology With Clinical Outcome.
Redefining Perineural Invasion: Integration of Biology With Clinical Outcome.
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DOI：
10.1016/j.neo.2018.04.005
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
D'Silva NJ
中科院分区：
文献类型：
--
作者：
Schmitd LB;Beesley LJ;Russo N;Bellile EL;Inglehart RC;Liu M;Romanowicz G;Wolf GT;Taylor JMG;D'Silva NJ
神经周围浸润（PNI）的诊断定义为至少33%的神经内或周围的癌症，导致选择鳞状细胞癌（SCC）的积极治疗。最近的机制研究表明，癌症和神经在身体接触之前相互作用。本研究的目的是探讨癌症-神经相互作用与临床结果的关系。对71例口腔鳞状细胞癌患者的活检标本进行苏木精-伊红染色和免疫组化（IHC;细胞角蛋白，S100，GAP 43，Tuj 1）染色。使用目前的标准，PNI检测增加了免疫组化。PNI患者的总生存率（OS）往往较差（P = 0.098）。最小肿瘤-神经距离小于5 μm的患者的OS显著较低（P = .011）。随着神经-肿瘤距离的增加，估计的相对死亡率下降;从距离等于零开始，死亡率逐渐下降，并在500 μm左右稳定下来。在PNI阴性患者中，神经直径与OS显著相关（HR 2.88，95%CI[1.11，7.49]）。在PNI阴性的神经中，较大的神经-肿瘤距离和较小的神经直径与较好的OS显著相关，即使调整了T分期和年龄（HR 0.82，95%CI [0.72，0.92]; HR 1.27，95%CI [1.00，1.62]）。GAP 43是神经元生长的标志物，在距离肿瘤较远的神经中，其染色程度低于Tuj 1（OR 0.76，95% CI[0.73，0.79]）;更多的GAP 43染色与PNI相关。一小组患者的研究结果表明，神经参数以外的PNI的存在可以影响结果，目前的PNI标准需要重新评估，以整合最近的生物学发现。
A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains. Using current criteria, PNI detection was increased with IHC. Overall survival (OS) tended to be poor for patients with PNI (P = .098). OS was significantly lower for patients with minimum tumor-nerve distance smaller than 5 μm (P = .011). The estimated relative death rate decreased as the nerve-tumor distance increased; there was a gradual drop off in death rate from distance equal to zero that stabilized around 500 μm. In PNI-negative patients, nerve diameter was significantly related to OS (HR 2.88, 95%CI[1.11,7.49]). Among PNI-negative nerves, larger nerve-tumor distance and smaller nerve diameter were significantly related to better OS, even when adjusting for T-stage and age (HR 0.82, 95% CI[0.72,0.92]; HR 1.27, 95% CI[1.00,1.62], respectively). GAP43, a marker for neuronal outgrowth, stained less than Tuj1 in nerves at greater distances from tumor (OR 0.76, 95% CI[0.73,0.79]); more GAP43 staining was associated with PNI. Findings from a small group of patients suggest that nerve parameters other than presence of PNI can influence outcome and that current criteria of PNI need to be re-evaluated to integrate recent biological discoveries.
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作者：
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