Pathogenic Biomarkers for Perineural Invasion in Adenoid Cystic Carcinoma

Abstract

Objectives:

Perineural invasion (PNI) has emerged as an adverse pathological feature of adenoid cystic carcinoma (ACC). Despite their importance, the local control factors involved in PNI remain unknown. Recent research has suggested that nerve growth factor (NGF) may be one of the important factors for PNI in other malignancies. Furthermore, in ACC, Myb overexpression related to the MYB–NFIB fusion gene has been correlated with PNI; however, this concept has been highly controversial. In this study, we examined the overexpression of NGF, its receptors (TrkA and p75NRT), and Myb in ACC cancer cells and investigated the relationship with PNI and local control.

Methods:

We retrospectively analyzed 47 patients with ACC who were surgically treated from 1991 to 2011. We reviewed NGF, TrkA, p75NRT, and Myb overexpression in the surgical specimens and examined the correlation with PNI, local control, and disease-specific survival.

Results:

The overexpression rates of NGF, TrkA, p75NRT, and Myb were 66%, 66%, 30%, and 57%, respectively. NGF and TrkA were significantly overexpressed in the PNI-positive group (NGF overexpression rate: PNI-positive vs PNI-negative, 88% vs 20%, P < .001; TrkA overexpression rate: PNI-positive vs PNI-negative, 81% vs 33%, P < .01). Moreover, patients with NGF overexpression had a significantly poorer 10-year local control rate (75% vs 13%, P < .05); however, p75NRT and Myb overexpression were not related to PNI.

Conclusions:

NGF and TrkA overexpression may contribute to PNI and cause local recurrence in ACC. However, Myb overexpression was not related to PNI in our analysis.