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

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.