HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Transcription factor snail1 expression and poor survival in pharyngeal squamous cell carcinoma

Anna Jouppila-Mättö1,4,5*, Hanna Tuhkanen1,2,3*, Ylermi Soini1,2,3, Matti Pukkila4,5, Mervi Närkiö-Mäkelä4,5, Reijo Sironen1,2,3, Ismo Virtanen†,6, Arto Mannermaa1,2,3 and Veli-Matti Kosma1,2,3

1Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland, 2Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland, 3Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland, 4Department of Otorhinolaryngology-Head and Neck Surgery, Kuopio University Hospital, Kuopio, Finland, 5Institute of Clinical Medicine, Otorhinolaryngology-Head and Neck Surgery, University of Eastern Finland, Kuopio, Finland and 6Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland
*Equal contribution.

Offprint requests to: Anna Jouppila-Mättö, Department of Otorhinolaryngology-Head and Neck Surgery, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland. e-mail: anna.jouppila-matto@kuh.fi


Summary. Snail1, a key regulator of epithelial-mesenchymal transition (EMT), plays an important role in tumour progression. Previous studies of snail1 have mainly focused on the epithelial tumour cells. The objective of this study was to evaluate the expression of snail1 protein in endothelial cells, stromal myofibroblasts and malignant epithelial cells of pharyngeal squamous cell carcinomas (PSCC), as well as its relation to clinicopathological features and survival. One hundred and ten tissue microarray samples were analyzed for snail1 expression using immunohistochemistry. In endothelial cells snail1 expression was observed in 51 (48%) of 107 cases and it predicted reduced disease specific survival (DSS) (p=0.009). In 49 (46%) tumour samples snail1 immunostaining was detected in stromal myofibroblasts and there was a tendency to poorer DSS in that group (p=0.067). Snail1 expression in endothelial cells and stromal myofibroblasts is also associated with hypopharyngeal tumours (p=0.01 and p=0.038 respectively), increasing T category (T3-4) (p=0.005, p=0.037 respectively) and poorer general condition of the patient (Karnofsky performance status score <70; p=0.029, p=0.039 respectively). Moreover endothelial expression correlated with advanced stage (III-IV) (p=0.005) and poorer differentiation (grade 2-3; p=0.012). In malignant epithelial cells snail1 immunostaining was detected in 75 of 110 cases (68%). Expression of the protein was more common in hypopharyngeal tumours (p=0.044). Snail1 positive tumours associated with a lower Karnofsky performance status score (p=0.039) and regional failure (p=0.042). Our findings indicate that snail1 protein expression in endothelial cells and to some extent also in tumour stromal myofibroblasts seems to be a predictor of poor survival in PSCC. The presence of snail1 protein in tumour microenvironment rather than in malignant epithelial tumour cells may induce tissue remodelling and tumour progression
. Histol Histopathol 26, 443-449 (2011)

Key words: Pharyngeal squamous cell carcinoma, Endothelial cell, Stromal myofibroblast, Snail1 protein, Prognosis, Epithelial-mesenchymal transition

DOI: 10.14670/HH-26.443