title: Transcription factor snail1 expression and poor survival in pharyngeal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland. anna.jouppila-matto@kuh.fi
authors.forename: Anna
authors.initials: A
authors.lastname: Jouppila-Mättö
authors.forename: Hanna
authors.initials: H
authors.lastname: Tuhkanen
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Matti
authors.initials: M
authors.lastname: Pukkila
authors.forename: Mervi
authors.initials: M
authors.lastname: Närkiö-Mäkelä
authors.forename: Reijo
authors.initials: R
authors.lastname: Sironen
authors.forename: Ismo
authors.initials: I
authors.lastname: Virtanen
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism; D010610:Pharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D017154:Stromal Cells / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors