title: Snail as a novel marker for regional metastasis in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Previous studies have shown Snail expression integral to the epithelial-mesenchymal transition during tumor progression. However, its behavior in clinical head and neck squamous cell carcinomas (HNSCCs) is yet undefined. We therefore sought to (1) investigate clinical and histopathologic characteristics of Snail-positive HNSCC and (2) understand the link between Snail and other commonly used HNSCC tumor markers.
  
  
  METHODS
  A retrospective case-control study was conducted.
  
  
  METHODS
  This study was conducted in a large-scale academic center.
  
  
  METHODS
  Of 51 consecutive HNSCC, 42 surgical resections were included.
  
  
  METHODS
  Two separate pathologists performed standard histopathologic reviews along with immunohistochemistries (Snail, E-cadherin, p16, epidermal growth factor receptor [EGFR]) and in situ hybridization (human papilloma virus [HPV]). Medical review for all cases was performed.
  
  
  RESULTS
  Twenty-two (52%) of 42 cases stained 4+ Snail (>75% staining). The remaining 20 cases were considered negative. Snail was strongly inversely related to E-cadherin expression (ρ = -0.69, P < .001), but statistically independent from HPV, p16, or EGFR expression. Snail(+) tumors were equally represented from each anatomic subsite. Snail(+) tumors were strongly associated with poor differentiation (P < .001) and basaloid classification (P = .004). Snail(+) tumors were also strongly associated with lymphovascular invasion (P = .02), but not perineural invasion. Ultimately, 11 (50%) of 22 of Snail(+) tumors demonstrated positive nodal metastasis and 11 (79%) of 14 node-positive cases were Snail(+) (P = .02).
  
  
  CONCLUSIONS
  This pilot study provides promising evidence of Snail' role as a molecular prognostic marker for HNSCC. Snail positivity is significantly predictive of poorly differentiated, lymphovascular invasive, as well as regionally metastatic tumors. Because Snail positivity appears independent of HPV, p16, and EGFR expression, Snail may prove to improve upon these markers' predictive limitations.
authors: Division of Head and Neck Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. amendelsohn@mednet.ucla.edu
authors: Abie H
authors: AH
authors: Mendelsohn
authors: Chi K
authors: CK
authors: Lai
authors: I Peter
authors: IP
authors: Shintaku
authors: Michael C
authors: MC
authors: Fishbein
authors: Katherine
authors: K
authors: Brugman
authors: David A
authors: DA
authors: Elashoff
authors: Elliot
authors: E
authors: Abemayor
authors: Steven M
authors: SM
authors: Dubinett
authors: Maie A
authors: MA
authors: St John
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D012189:Retrospective Studies; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D066246:ErbB Receptors