Autonomic nervous infiltration positively correlates with pathological risk grading and poor prognosis in patients with lung adenocarcinoma

Abstract

BACKGROUND: Perineural invasion has been found in several types of human tumors, and is associated with poor prognosis; however, few studies have examined perineural invasion in lung cancer. We evaluated the relationship between autonomic nervous densities, pathological risk grading, and prognosis in patients with lung adenocarcinoma (LADC). METHODS: Neural fiber expression was examined by immunofluorescence in resected lung specimens in control patients (n = 30), and low-risk (n = 22), and high-risk LADC patients (n = 43). The nerve densities of normal lung tissue and abnormal lung tissues in the tumor and surrounding tissues were evaluated by a semi-quantitative score method. RESULTS: Increased sympathetic fibers mainly infiltrated the paratumoral area, while increased parasympathetic fibers were largely restricted to the tumor (paratumor vs. tumor, P = 0.000 in high, P = 0.034 in low; each). In addition, high-risk patients presented the highest density of neural fibers, followed by low-risk and control patients ( P = 0.000; each). In Kaplan-Meier survival analysis, the densities of sympathetic fibers in paratumoral tissue and parasympathetic fibers in the tumor, respectively, correlated with poor recurrence-free survival in patients who were not treated with adjuvant therapy ( P < 0.001; each). Further multivariate analysis showed that these two factors were associated with poor prognosis in all LADC patients ( P = 0.024 sympathetic fibers; P = 0.037 parasympathetic fibers). CONCLUSION: These findings reveal a positive correlation between nervous infiltration and risk of poor prognosis in patients with LADC.