title: Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor β receptor type II as prognostic factors for colorectal cancer: results of a 10-year prospective study using tissue microarray analysis.
abstract: BACKGROUND
  The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.
  
  
  METHODS
  We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.
  
  
  RESULTS
  Minichromosome maintenance complex component 2 (MCM2) and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis (HR = 0.63, 95%CI: 0.46 - 0.86). Cyclin A expression above the median predicted an improved patient prognosis (HR = 0.71, 95%CI: 0.53 - 0.95). For mismatch repair deficiency and transforming growth factor β receptor type II (TGFBRII) overexpression there was a borderline association with a poorer prognosis (HR = 0.69, 95%CI: 0.46 - 1.04 and HR = 2.11, 95%CI: 1.02 - 4.40, respectively). No apparent associations were found for other markers.
  
  
  CONCLUSIONS
  This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. dbzhao2003@sina.com
authors.forename: Dong-bing
authors.initials: DB
authors.lastname: Zhao
authors.forename: Ian
authors.initials: I
authors.lastname: Chandler
authors.forename: Zheng-ming
authors.initials: ZM
authors.lastname: Chen
authors.forename: Hong-chao
authors.initials: HC
authors.lastname: Pan
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
authors.forename: Yong-fu
authors.initials: YF
authors.lastname: Shao
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D053843:DNA Mismatch Repair / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D019925:Cyclin A; D019394:Ki-67 Antigen; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II