title: SIP1 predicts progression and poor prognosis in pharyngeal squamous cell carcinoma.
abstract: The epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis that enables tumor cells to invade and metastasize. The transcription factors SIP1, SLUG, ZEB1, SNAI1, and TWIST are fundamental in regulating EMT. We investigated the relationships between several clinicopathological variables, prognosis, and SIP1, SLUG, or ZEB1 in a retrospective pharyngeal squamous cell carcinoma (PSCC) cohort.
  
  
  
  Immunohistochemistry was used to evaluate the expression of SIP1, SLUG, and ZEB1 in 108 tumor samples from a retrospective cohort of patients with PSCC.
  
  
  
  Tumors with positive epithelial SIP1 immunostaining were more advanced (SIII-IV, p=0.02) and had more lymph node metastases (p=0.04) than SIP1-negative tumors. Tumors with positive stromal staining of SIP1 relapsed more often than SIP1-negative tumors (p=0.007). Negative SIP1 immunoreactivity correlated significantly with better disease-specific survival (DSS) and better overall survival (OS) (p=0.012 and p=0.003 for epithelial reactivity, p=0.018 and p=0.003 for stromal reactivity, respectively). Lack of epithelial SIP1 expression remained an independent and favorable prognostic factor in a Cox proportional hazards model (p=0.046), together with high Karnofsky performance status score and low T class (p<0.001 for both). Co-expression of SNAI1, TWIST, and SIP1 in tumor epithelium predicted even shorter DSS than SIP1 expression alone (p<0.001) in the present study cohort.
  
  
  
  SIP1 is related to cancer progression and appears to be an independent prognostic factor in PSCC.
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, and Department of Otorhinolaryngology- Head and Neck Surgery, Kuopio University Hospital, and Institute of Clinical Medicine, Otorhinolaryngology- Head and Neck Surgery, University of Easter, Kuopio, Finland. anna.jouppila-matto@uef.fi.
authors.forename: Anna
authors.initials: A
authors.lastname: Jouppila-Mättö
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, and Department of Clinical Pathology, Imaging center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, and Department of Clinical Pathology, Imaging center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Sironen
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, and Department of Clinical Pathology, Imaging center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, and Department of Clinical Pathology, Imaging center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.affiliation: Department of Otorhinolaryngology- Head and Neck Surgery, Kuopio University Hospital, and Institute of Clinical Medicine, Otorhinolaryngology- Head and Neck Surgery, University of Eastern Finland, Kuopio, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Pukkila
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010610:Pharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: C108381:GEMIN2 protein, human; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1