神经生长因子信号作为腺样囊性癌中神经周围浸润的潜在致病生物标志物

Nerve Growth Factor Signals as Possible Pathogenic Biomarkers for Perineural Invasion in Adenoid Cystic Carcinoma.

作者信息

Kobayashi Kenya, Ando Mizuo, Saito Yuki, Kondo Kenji, Omura Go, Shinozaki-Ushiku Aya, Fukayama Masashi, Asakage Takahiro, Yamasoba Tatsuya

机构信息

Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan Department of Head and Neck Oncology, National Cancer Center Hospital, Tokyo, Japan

Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.

出版信息

Otolaryngol Head Neck Surg. 2015 Aug;153(2):218-24. doi: 10.1177/0194599815584762. Epub 2015 May 12.

DOI:10.1177/0194599815584762

PMID:25968060

Abstract

OBJECTIVE

The molecular mechanisms underlying perineural invasion (PNI)-a characteristic pathological feature of adenoid cystic carcinoma (ACC)-remain largely unclear. Recently, nerve growth factor (NGF) has been implicated in perineural invasion in certain malignancies. Overexpression of Myb related to the MYB-NFIB fusion gene in ACC has also been correlated with perineural invasion and survival. However, this concept is controversial. The aim of this study was to examine the expression of NGF together with its receptors, tropomyosin receptor kinase A (TrkA) and p75NRT, and Myb in ACC and assess their relationship with perineural invasion and survival.

STUDY DESIGN

Case series with chart review.

SETTING

The University of Tokyo Hospital.

SUBJECTS AND METHODS

We retrospectively analyzed 37 patients with ACC surgically treated from 1991 to 2011. We examined expression levels of NGF, TrkA, p75NRT, and Myb in the ACC specimens and their correlations with PNI and prognosis.

RESULTS

NGF, TrkA, p75NRT, and Myb overexpression rates were 65%, 65%, 30%, and 62%, respectively. Pearson product-moment correlation coefficient revealed a strong correlation between NGF/TrkA immunostaining and PNI (NGF: r = 0.68, P < .0001; TrkA: r = 0.53, P = .0007). Moreover, NGF overexpression was significantly associated with worse 8-year local control rate (27% vs 80%, P = .005). However, p75NRT and Myb expression was related to neither perineural invasion nor survival.

CONCLUSION

Our findings demonstrated that NGF and TrkA overexpression, but not Myb and p75NRT overexpression, may contribute to PNI and thus cause local recurrence in patients with ACC.

摘要

目的

神经周围浸润（PNI）是腺样囊性癌（ACC）的一个典型病理特征，其潜在分子机制仍不清楚。最近，神经生长因子（NGF）被认为与某些恶性肿瘤的神经周围浸润有关。ACC中与MYB-NFIB融合基因相关的Myb过表达也与神经周围浸润和生存相关。然而，这一观点存在争议。本研究旨在检测ACC中NGF及其受体原肌球蛋白受体激酶A（TrkA）和p75NRT以及Myb的表达，并评估它们与神经周围浸润和生存的关系。

研究设计

病例系列研究并进行图表回顾。

研究地点

东京大学医院。

研究对象与方法

我们回顾性分析了1991年至2011年接受手术治疗的37例ACC患者。我们检测了ACC标本中NGF、TrkA、p75NRT和Myb的表达水平，以及它们与PNI和预后的相关性。

结果

NGF、TrkA、p75NRT和Myb的过表达率分别为65%、65%、30%和62%。Pearson积矩相关系数显示NGF/TrkA免疫染色与PNI之间存在强相关性（NGF：r = 0.68，P <.0001；TrkA：r = 0.53；P =.0007）。此外，NGF过表达与较差的8年局部控制率显著相关（27%对80%，P =.005）。然而，p75NRT和Myb表达与神经周围浸润和生存均无关。