title: Co-existence of cyclin D1 and vascular endothelial growth factor protein expression is a poor prognostic factor for UICC stage I-III colorectal cancer patients after curative resection.
abstract: BACKGROUND
  Angiogenesis plays an important role in the progression of colorectal cancer (CRC). Studies have indicated vascular endothelial growth factor (VEGF) is the predominant angiogenic factor. Cyclin D1 (CCND1) induces production of VEGF and is required for migration of blood vessels. Our aim was to determine the roles of CCND1 and VEGF overexpression in CRC patients.
  
  
  METHODS
  We analyzed clinicopathological features, VEGF and CCND1 expressions by immunohistochemical (IHC) staining in 100 stage I-III CRC patients (44 were postoperative relapsed; 56 were postoperative non-relapsed) to determine the correlation between clinicopathologic features and co-existence of CCND1 and VEGF. Furthermore, the clinical outcomes of co-existence of CCND1 and VEGF were investigated.
  
  
  RESULTS
  Multivariate analysis showed vascular invasion (P = 0.019), VEGF overexpression (P = 0.033), and high postoperative serum carcinoembryonic antigen (CEA) levels (P = 0.022) were independent predictors of postoperative relapse. Co-existence of CCND1 and VEGF overexpression had significantly poorer disease-free survival rates (P  = 0.004) and overall survival rates (P = 0.001) than other phenotypes.
  
  
  CONCLUSIONS
  Co-existence of CCND1 and VEGF overexpression would potentially assist in TNM staging systems to predict the prognosis of these patients who would benefit from intensive follow-up and therapeutic programs.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Tsai
authors.forename: Yung-Sung
authors.initials: YS
authors.lastname: Yeh
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Chang
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Yang
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Suh-Hang
authors.initials: SH
authors.lastname: Juo
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D012007:Rectum / Q000601:surgery*; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1