title: Integrin α11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression.
abstract: BACKGROUND
  Cancer-associated fibroblasts (CAFs) were shown to be important for tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their heterogeneity and lack of specific markers is increasingly recognized. Integrin α11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker.
  
  
  OBJECTIVE
  To investigate integrin α11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (α-SMA), in HNSCC.
  
  
  METHODS
  Fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples from healthy volunteers (n = 24), oral lichen planus (OLP) (n = 32) and HNSCC (n = 106) were collected together with clinical data after ethical approval. Immunohistochemistry to detect integrin α11 and α-SMA was performed on FF and FFPE samples. qPCR for integrin α11 (ITGA11) and α-SMA (ACTA2) was performed on FF samples. Data were analysed using chi-square test and Kaplan-Meier survival analysis.
  
  
  RESULTS
  Significantly higher levels of integrin α11 and α-SMA at both protein and mRNA levels were found in HNSCC vs. normal controls and OLP. A strong correlation was found between integrin α11 and α-SMA expression, and double staining showed their colocalization. Both integrin α11 and α-SMA were detected surrounding metastatic islands. Expression of α-SMA at tumour front but not tumour centre correlated with patient survival.
  
  
  CONCLUSIONS
  Integrin α11 was overexpressed in HNSCC stroma and colocalized with α-SMA. Expression of α-SMA at tumour front but not tumour centre had prognostic value for survival, pinpointing the importance of assessing tumour front when evaluating stromal molecules as prognostic biomarkers.
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Centre for International Health, University of Bergen, Bergen, Norway.
authors.forename: Himalaya
authors.initials: H
authors.lastname: Parajuli
authors.affiliation: Centre for Clinical & Diagnostic Oral Sciences, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: Muy-Teck
authors.initials: MT
authors.lastname: Teh
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Siren
authors.initials: S
authors.lastname: Abrahamsen
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Christoffersen
authors.affiliation: Department of Oral Surgery, Institute of Clinical Dentistry, University of Bergen, Bergen, Norway.|Department of Maxillofacial Surgery, Head and Neck Clinic, Haukeland University Hospital, Bergen, Norway.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Neppelberg
authors.affiliation: Department of Maxillofacial Surgery, Head and Neck Clinic, Haukeland University Hospital, Bergen, Norway.|Department of Ear-Nose-and-Throat Surgery, Head and Neck Clinic, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stein
authors.initials: S
authors.lastname: Lybak
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Tarig
authors.initials: T
authors.lastname: Osman
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Anne Chr
authors.initials: AC
authors.lastname: Johannessen
authors.affiliation: Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Biomatrix Research Group, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Donald
authors.initials: D
authors.lastname: Gullberg
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kathrine
authors.initials: K
authors.lastname: Skarstein
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Centre for International Health, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Daniela Elena
authors.initials: DE
authors.lastname: Costea
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000199:Actins; C121535:ITGA11 protein, human; D039001:Integrin alpha Chains
keywords: ACTA2; ITGA11; alpha smooth muscle actin; immunohistochemistry; integrin α11; tumour stroma