Snail Expression Is a Rare Event in Oral Squamous Cell Carcinoma Associated with Features of Poor Prognosis
J Schwock, G Bradley, B Perez-Ordonez, DW Hedley, JC Irish, WR Geddie. University of Toronto, Toronto, ON, Canada; Ontario Cancer Institute, Toronto, ON, Canada
Background: Epithelial-mesenchymal transition (EMT) is an embryological process that can be aberrantly reactivated in cancer and is thought to contribute to epithelial tumor progression. Snail is one of several transcriptional repressors of the cell adhesion molecule E-cadherin capable of EMT induction. Loss of epithelial characteristics by EMT potentially contributes to invasion and metastasis of oral squamous cell carcinoma (OSCC) and might be associated with over-expression of focal adhesion kinase (FAK), a signalling molecule involved in cell migration, and loss of p63, a marker of squamous origin.
Design: We examined the expression of Snail, E-cadherin, FAK and p63 in formalin-fixed paraffin-embedded tissue from 46 patients diagnosed with OSCC and obtained outcome data from clinical files. Primary tumors and one lymph node metastasis of each N+ case (26/46) were stained by immunohistochemistry. Two commercially available Snail antibodies were used after evaluation of their specificity. Scoring was performed on full sections to account for heterogeneity and rare/focal expression of the parameters of interest.
Results: Snail expression (nuclear, 5% tumor cells positive) was observed in 10 primary tumors and 5 metastases. 30 patients had at least rare individual tumor cells with Snail positivity whereas all cases had occasional to abundant Snail-positive stroma cells. E-cadherin loss was observed in 29/46 cases (63%) and was associated with presence of lymph node metastases (21/29 [72%] E-cadherin negative, 5/17 [29%] E-cadherin positive; p<0.05 Fisher's exact test). Cytoplasmic FAK was over-expressed in 10 (22%) cases and associated with tumor recurrence/new primary (9/10 [90%] FAKc high, 16/36 [44%] FAKc low expression; p<0.05). Two N+ cases showed a distinct sarcomatoid component within the primary tumor with Snail+/FAK+/E-cadherin/p63 phenotype. The metastasis of one case displayed a Snail, the other a Snail+ phenotype.
Conclusions: We conclude that Snail-associated EMT occurs as a rare event in OSCC and can indicate the presence of a sarcomatoid component. Absence of p63 in primary tumor or metastasis does not exclude squamous origin in the context of EMT. Additional transcriptional repressors of E-cadherin should be examined for their contribution to OSCC progression.
Category: Head & Neck
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 172, Monday Morning