title: The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma.
abstract: OBJECTIVE
  Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the genes of a recently validated LNM-predicting gene expression profile in OSCC. This study evaluates their clinicopathological role and value as biomarkers in OSCC.
  
  
  METHODS
  Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papillomavirus (HPV) status was determined by an algorithm for HPV-16. Protein expression for KLK5, KLK7 and SPINK5 was semi-quantitatively determined in all 83 tumours by immunohistochemistry. All expression data were correlated with clinicopathological parameters.
  
  
  RESULTS
  Concurrent loss of KLK5 and KLK7 correlates with worse disease-specific and overall survival (DSS and OS). Multivariate analysis proved that co-expression is an independent prognostic factor for DSS (p = 0.029) and OS (p = 0.001).
  
  
  CONCLUSIONS
  This report demonstrates that concurrent loss of KLK5 and KLK7 associates with a poor clinical outcome in OSCC and could therefore serve as prognostic marker in this disease.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Frank K J
authors.initials: FK
authors.lastname: Leusink
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: M H
authors.initials: MH
authors.lastname: Frank
authors.forename: R
authors.initials: R
authors.lastname: Broekhuizen
authors.forename: W
authors.initials: W
authors.lastname: Braunius
authors.forename: S R
authors.initials: SR
authors.lastname: van Hooff
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
authors.forename: R
authors.initials: R
authors.lastname: Koole
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000302:isolation & purification; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality* / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins