title: Lack of claudin-7 is a strong predictor of regional recurrence in oral and oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Adequate treatment of oral and oropharyngeal squamous cell carcinoma (OSCC) is dependent on correctly predicting the presence of lymph node metastases. Current methods to diagnose nodal metastases partly result in overtreatment with associated morbidity and undertreatment with decreased disease-free survival. E-cadherin has been studied extensively as potential marker for lymph node metastases. EpCAM and claudin-7 have a functional relationship with E-cadherin, forming a complex that promotes tumourigenicity in vitro. We hypothesize that the co-expression patterns of these related molecules is a better prognostic marker for nodal status and regional recurrences.
  
  
  METHODS
  We constructed separate tissue microarrays of tumour centre and tumour invasive front of 227 OSCC with complete clinicopathological and follow-up data, including HPV status, and performed immunohistochemistry for these molecules.
  
  
  RESULTS
  Lack of E-cadherin and presence of cytoplasmic EpCAM expression in the tumour front were predictive for nodal metastasis, but no co-expression pattern was found clinically relevant. Lack of claudin-7 in the tumour centre was highly and independently predictive for shorter regional disease-free survival (HR=0.19; 95%CI: 0.06-0.62) and disease-specific survival (HR=0.43; 95%CI: 0.21-0.87). High-risk HPV was not associated with any marker.
  
  
  CONCLUSIONS
  The expression of E-cadherin and EpCAM, depending on the specific tumour sublocalization, is predictive for nodal status. However, co-expression did not improve the prediction of nodal status, indicating that the proposed in vitro complex is not functional in clinical samples. Additionally, lack of claudin-7 expression in the tumour centre may be used to identify patients with increased risk for regional recurrence.
authors: Dept. of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700RB Groningen, The Netherlands; Dept. of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: L.J.Melchers@umcg.nl.
authors: L J
authors: LJ
authors: Melchers
authors: L
authors: L
authors: Bruine de Bruin
authors: U
authors: U
authors: Schnell
authors: L
authors: L
authors: Slagter-Menkema
authors: M F
authors: MF
authors: Mastik
authors: G H
authors: GH
authors: de Bock
authors: B A C
authors: BA
authors: van Dijk
authors: B N G
authors: BN
authors: Giepmans
authors: B F A M
authors: BF
authors: van der Laan
authors: J E
authors: JE
authors: van der Wal
authors: J L N
authors: JL
authors: Roodenburg
authors: E
authors: E
authors: Schuuring
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D057167:Claudins / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism*; D009959:Oropharyngeal Neoplasms / Q000378:metabolism*; D011379:Prognosis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C473255:CLDN7 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D057167:Claudins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: Cell adhesion; Claudin-7; E-cadherin; EpCAM; Head and neck cancer; Nodal metastasis; Oral cancer; Regional recurrence