title: Expression of CREB in primary pterygium and correlation with cyclin D1, ki-67, MMP7, p53, p63, Survivin and Vimentin.
abstract: OBJECTIVE
  Ultraviolet (UV) B irradiation induces gene expression that leads to skin cancer. Among the transcription factors induced by UVB radiation exposure, the cyclic AMP response element-binding protein (CREB) is significant. Since several factors downstream of CREB signaling are known to be involved in pterygium pathogenesis, we investigated CREB expression in pterygial and human conjunctival tissues to evaluate if a similar expression pattern is present. Moreover, we analyzed the correlation with CREB expression and other known pterygium markers.
  
  
  METHODS
  Primary pterygium samples and normal bulbar conjunctivas surgically removed were analyzed. Formalin-fixed, paraffin-embedded tissues were stained by immunohistochemistry with anti-CREB, anti-vimentin, anti-ki-67, anti-survivin, anti-MMP7, anti-p63, anti-cyclin D1, or anti-p53 antibodies.
  
  
  RESULTS
  94.4% of pterygium samples were positive for CREB with a significant difference compared to the control group (p = 0.002). The staining was localized in the epithelium and absent in the stroma. An increased expression was found for cyclin D1 (p = 0.019), ki-67 (p = 0.005), vimentin (p = 0.003), survivin (p < 0.001), p63 (p = 0.003), and MMP7 (p = 0.002). CREB expression showed a significant correlation with cyclin D1 (ρ = 0.49; p = 0.035), ki-67 (ρ = 0.61; p = 0.007), and p53 (ρ = 0.57; p = 0.013) in pterygium.
  
  
  CONCLUSIONS
  These results permit to hypothesize that CREB is involved in pterygium pathogenesis. Since various molecules have been discovered to inhibit CREB, these data could be of interest for pterygium treatment.
authors.affiliation: Department of Medicine and Ageing Science, Opthalmology Clinic, University 'G. d'Annunzio' of Chieti-Pescara, Chieti/Pescara, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nubile
authors.forename: Claudia
authors.initials: C
authors.lastname: Curcio
authors.forename: Manuela
authors.initials: M
authors.lastname: Lanzini
authors.forename: Roberta
authors.initials: R
authors.lastname: Calienno
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mastropasqua
authors.forename: Marta
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mastropasqua
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011625:Pterygium / Q000378:metabolism* / Q000601:surgery; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D015415:Biomarkers; C530104:CCND1 protein, human; C081876:CKAP4 protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D005136:Eye Proteins; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D014746:Vimentin; D019938:Cyclin D1; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7