title: Perineural growth in head and neck squamous cell carcinoma: a review.
abstract: Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor cells inside the neural space seen on histological or imaging evaluations. Little is known about molecular mechanisms involved in the growth and spread of tumor cells in neural spaces. The poor prognosis associated with perineural growth and lack of targeted approaches necessitates the study of molecular factors involved in communication between tumor and neural cells. Perineural growth rates, shown to be as high as 63% in head and neck squamous cell carcinoma (HNSCC), correlate with increased local recurrence and decreased disease-free survival. Here we describe the literature on perineural growth in HNSCC. In addition, we discuss factors implicated in perineural growth of cancer. These factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 and -4, glial cell-line derived neurotrophic factor (GDNF), the neural cell adhesion molecule (NCAM), substance P (SP), and chemokines. We also explore the literature on membrane receptors, including the Trk family and the low-affinity nerve growth factor receptor. This review highlights areas for further study of the mechanisms of perineural invasion which may facilitate the identification of therapeutic targets in HNSCC.
authors.affiliation: Departments of Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, KS, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Roh
authors.affiliation: Departments of Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, KS, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Muelleman
authors.affiliation: Pathology and Laboratory Medicine, University of Kansas Medical Center and University of Kansas Cancer Center, KS, United States.
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
authors.affiliation: Departments of Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, KS, United States; Cancer Biology, University of Kansas Medical Center and University of Kansas Cancer Center, KS, United States; Anatomy and Cell Biology, University of Kansas Medical Center and University of Kansas Cancer Center, KS, United States. Electronic address: sthomas7@kumc.edu.
authors.forename: Sufi M
authors.initials: SM
authors.lastname: Thomas
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D009362:Neoplasm Metastasis
keywords: Chemokines; Neurotrophic factors; Neurotrophin; Perineural growth; Perineural invasion; Squamous cell carcinoma