title: SNAI1 expression and the mesenchymal phenotype: an immunohistochemical study performed on 46 cases of oral squamous cell carcinoma.
abstract: BACKGROUND
  SNAI1 can initiate epithelial-mesenchymal transition (EMT), leading to loss of epithelial characteristics and, in cancer, to invasion and metastasis. We hypothesized that SNAI1 reactivation occurs in oral squamous cell carcinoma (OSCC) where it might also be associated with focal adhesion kinase (FAK) expression and p63 loss.
  
  
  METHODS
  Immunohistochemistry was performed on 46 tumors and 26 corresponding lymph node metastases. Full tissue sections were examined to account for rare and focal expression. Clinical outcome data were collected and analyzed.
  
  
  RESULTS
  SNAI1-positivity (nuclear, >/= 5% tumor cells) was observed in 10 tumors and 5 metastases (n = 12 patients). Individual SNAI1(+) tumor cells were seen in primary tumors of 30 patients. High level SNAI1 expression (>10% tumor cells) was rare, but significantly associated with poor outcome. Two cases displayed a sarcomatoid component as part of the primary tumor with SNAI1(+)/FAK(+)/E-cadherin(-)/p63(-) phenotype, but disparate phenotypes in corresponding metastases. All cases had variable SNAI1(+) stroma. A mesenchymal-like immunoprofile in primary tumors characterized by E-cadherin loss (n = 29, 63%) or high cytoplasmic FAK expression (n = 10, 22%) was associated with N(+) status and tumor recurrence/new primary, respectively.
  
  
  CONCLUSIONS
  SNAI1 is expressed, although at low levels, in a substantial proportion of OSCC. High levels of SNAI1 may herald a poor prognosis and circumscribed SNAI1 expression can indicate the presence of a sarcomatoid component. Absence of p63 in this context does not exclude squamous tumor origin. Additional EMT inducers may contribute to a mesenchymal-like phenotype and OSCC progression.
authors.affiliation: Department of Laboratory Medicine & Pathobiology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada. william.geddie@uhn.on.ca.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schwock
authors.forename: Grace
authors.initials: G
authors.lastname: Bradley
authors.forename: James C
authors.initials: JC
authors.lastname: Ho
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Irish
authors.forename: William R
authors.initials: WR
authors.lastname: Geddie