title: Nerve Growth Factor Signals as Possible Pathogenic Biomarkers for Perineural Invasion in Adenoid Cystic Carcinoma.
abstract: 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.
  
  
  METHODS
  Case series with chart review.
  
  
  METHODS
  The University of Tokyo Hospital.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan Department of Head and Neck Oncology, National Cancer Center Hospital, Tokyo, Japan kenyajp@hotmail.com.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Mizuo
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Omura
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shinozaki-Ushiku
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Asakage
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D003528:Carcinoma, Adenoid Cystic / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009414:Nerve Growth Factors / Q000032:analysis*; D011379:Prognosis; D020917:Receptor, trkA / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D009414:Nerve Growth Factors; D020917:Receptor, trkA
keywords: Myb; NGF; TrkA; adenoid cystic carcinoma; perineural invasion