title: Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas.
  
  
  METHODS
  C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied.
  
  
  RESULTS
  C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal-adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 ± 0.07 vs 0.04 ± 0.03 μg ml(-1) , P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55-0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 ± 0.59 vs 1.09 ± 0.39 μg ml(-1) , P = 0.232).
  
  
  CONCLUSIONS
  C4d-containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC.
authors.affiliation: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra's Health Research Institute (IDISNA), Pamplona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Ajona
authors.affiliation: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra's Health Research Institute (IDISNA), Pamplona, Spain.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pajares
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Chiara
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: Rodrigo
authors.affiliation: Molecular Oncology Laboratory, Fundación para la Investigación del Hospital General Universitario de Valencia, Valencia, Spain.|Department of Biotechnology, Universitat Politècnica de Valencia, Valencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Jantus-Lewintre
authors.affiliation: Department of Medicine, University of Valencia, Valencia, Spain.|Department of Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Camps
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Suarez
authors.affiliation: Department of Oral Medicine, University of Valencia, and Service of Stomatology and Maxillofacial Surgery, University General Hospital, Valencia, Spain.
authors.forename: J V
authors.initials: JV
authors.lastname: Bagán
authors.affiliation: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra's Health Research Institute (IDISNA), Pamplona, Spain.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Montuenga
authors.affiliation: Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain.|Navarra's Health Research Institute (IDISNA), Pamplona, Spain.|Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pio
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000737:chemistry* / Q000473:pathology*; D015935:Complement C4b / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007972:Leukoplakia, Oral / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood / Q000737:chemistry* / Q000473:pathology*; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D012372:ROC Curve; D012463:Saliva / Q000737:chemistry; D047368:Tumor Burden
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: C4d; biomarker; complement system; diagnosis; head and neck cancer; oral cancer; saliva; squamous cell carcinoma