title: Predictive role of thymidine phosphorylase expression in patients with colorectal cancer and its association with angiogenesis-related proteins and extracellular matrix components.
abstract: BACKGROUND
  Thymidine phosphorylase (TYMP) is an angiogenic factor that has potent chemotactic activity for endothelial cells and is involved in 5-fluorouracil (5-FU) metabolism. In colorectal cancer (CRC), previous studies evaluating the relationship between TYMP expression and clinicopathological features have yielded inconsistent results. The aim of this study was to investigate the prognostic value of TYMP, its association with other angiogenic factors, proliferation markers and, to our knowledge, for the first time its relationship with extracellular matrix components.
  
  
  METHODS
  Formalin-fixed, paraffin-embedded specimens from 97 patients with CRC were immunostained for TYMP, vascular endothelial growth factor (VEGF), microvascular density (CD34), proliferation marker (Ki-67), proliferating cell nuclear antigen (PCNA), p53 oncoprotein and extracellular matrix components (collagen type IV, fibronectin, tenascin and laminin). Survival curves were calculated with the Kaplan-Meier method.
  
  
  RESULTS
  Immunoreactivity was observed in the cytoplasm (cyt) and nucleus (n) of the tumor cells, as well in the stroma (st), endothelium and tumor-associated macrophages. High TYMPcyt expression was observed in 7.2% of the cases, moderate in 22.7% and weak in 59.9%, while 10.3% were negative. High TYMPst expression was observed in 58.8% of the cases. TYMPcyt expression was correlated with the VEGF expression of tumor cells and VEGF expression of vessels (p=0.014 and p=0.022, respectively). TYMPst expression was correlated with VEGF expression and tenascin (p=0.014 and p=0.011, respectively). Patients with higher TYMPcyt expression had a more favorable overall survival (p=0.041) in univariate analysis compared to patients without TYMP expression.
  
  
  CONCLUSIONS
  These findings suggest that TYMP plays an important role in angiogenesis, extracellular matrix remodeling and in the prognosis of patients with CRC, but further studies are needed to clearly define its role in CRC.
authors.affiliation: Department of Forensic Pathology, Medical School, University of Ioannina, Greece. amitselo@cc.uoi.gr
authors.forename: Antigony
authors.initials: A
authors.lastname: Mitselou
authors.forename: Elli
authors.initials: E
authors.lastname: Ioachim
authors.forename: Urania
authors.initials: U
authors.lastname: Skoufi
authors.forename: Christos
authors.initials: C
authors.lastname: Tsironis
authors.forename: Konstantinos E
authors.initials: KE
authors.lastname: Tsimogiannis
authors.forename: Christina
authors.initials: C
authors.lastname: Skoufi
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vougiouklakis
authors.forename: Evagelos
authors.initials: E
authors.lastname: Briasoulis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D013939:Thymidine Phosphorylase; D005472:Fluorouracil