Perineural invasion and expression of nerve growth factor can predict the progression and prognosis of oral tongue squamous cell carcinoma

Background: Perineural invasion (PNI) and nerve growth factor (NGF) expression are found to be significantly associated with the progression and/or prognosis of several human cancers. Methods: Immunohistochemical staining for S-100 and NGF proteins was performed to assess the PNI and NGF expression level in 116 oral tongue squamous cell carcinoma (OTSCC) specimens, respectively. Results: The PNI rate increased from 22% of the original pathological report, through 39% after reevaluation of hematoxylin and eosin-stained tissue sections, to 51% with the help of anti-S-100 immunostaining. The positive PNI was significantly associated with larger tumor size (P = 0.033), positive lymph node metastasis (P = 0.001), advanced clinical stage (P < 0.001), greater tumor thickness (P < 0.001), close or positive section margin (P = 0.013), and higher grade of cancer invasion front pattern (P < 0.001). Moreover, the high NGF expression level was significantly correlated with larger tumor size (P = 0.009), positive lymph node metastasis (P = 0.004), advanced clinical stage (P < 0.001), greater tumor thickness (P = 0.005), close or positive section margin (P = 0.030), and the positive PNI (P = 0.009). In addition, OTSCC patients with positive PNI or high NGF expression level had significantly worse overall survival than those with negative PNI or low NGF expression level, respectively. Conclusions: Anti-S-100 immunostaining is an effective technique to detect occult PNI. Both the positive PNI and NGF expression level are valuable biomarkers that can predict the progression of OTSCC and prognosis of OTSCC patients. ? 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.