title: Expression and prognostic value of transcription factor PROX1 in colorectal cancer.
abstract: BACKGROUND
  PROX1 is a specific target of the β-catenin/TCF pathway in the intestinal epithelium. It acts as a regulator of progression from a benign to a highly dysplastic phenotype in colorectal tumours. However, the clinical significance of PROX1 expression is not known.
  
  
  METHODS
  We studied the prognostic value of immunohistochemical expression of PROX1 in a series of 517 patients with colorectal cancer (CRC).
  
  
  RESULTS
  The majority of the tumour samples expressed PROX1 (91%, 471 out of 517). High PROX1 expression was associated with a poor grade of tumour differentiation (P<0.0001). In the subgroup of patients with colon cancer, high PROX1 expression was associated with unfavourable colorectal cancer-specific survival (CCSS) as compared with low PROX1 expression (CCSS 47% vs 62%; P=0.045; RR 1.47). The association between high PROX1 and poor outcome was further strengthened in female colon cancer patients (CCSS 38% vs 63%; P=0.007; RR 2.02). Nonetheless, in multivariate survival analysis PROX1 expression was not retained as an independent prognostic factor.
  
  
  CONCLUSIONS
  High PROX1 expression is associated with a poor grade of tumour differentiation, and, in colon cancer patients, also with less favourable patient outcome. Our results strengthen the previous preclinical observations that PROX1 has a role in tumour progression in CRC.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki FIN-00029 HUS, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Skog
authors.forename: P
authors.initials: P
authors.lastname: Bono
authors.forename: M
authors.initials: M
authors.lastname: Lundin
authors.forename: J
authors.initials: J
authors.lastname: Lundin
authors.forename: J
authors.initials: J
authors.lastname: Louhimo
authors.forename: N
authors.initials: N
authors.lastname: Linder
authors.forename: T V
authors.initials: TV
authors.lastname: Petrova
authors.forename: L C
authors.initials: LC
authors.lastname: Andersson
authors.forename: H
authors.initials: H
authors.lastname: Joensuu
authors.forename: K
authors.initials: K
authors.lastname: Alitalo
authors.forename: C H
authors.initials: CH
authors.lastname: Haglund
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein