title: Expression of cell cycle regulators p21 and p27 as predictors of disease outcome in colorectal carcinoma.
abstract: BACKGROUND
  Recent studies suggest that aberrations in cell cycle checkpoint controllers are a common feature in human malignancies and predict prognosis independent of stage.
  
  
  OBJECTIVE
  This study correlated two cell cycle regulators (p27 and p21) with clinical and pathological variables in colorectal cancer (CRC) patients to assess their role as prognostic factors.
  
  
  METHODS
  A series of 65 CRC patients were analyzed for p27 and p21 expression in their tumors using immunohistochemistry.
  
  
  RESULTS
  Forty-six percent of tumors showed positive nuclear p27 expression, whereas 72% of cases were completely p21 negative. There were no significant correlations between p27 and p21 expression and gender, age, lymph node involvement, stage, and grade. However, p27 (but not p21) expression revealed highly significant correlation with tumor location (p < 0.01), depth of invasion (p < 0.03), and lympho-vascular invasion (p < 0.02). Tumors with high p27 expression showed a higher recurrence rate than tumors with no expression (p < 0.03). In Kaplan-Meier survival analysis, there was a significant (p = 0.046) difference in disease-free survival (DFS) between p27-positive and p27-negative tumors in favor of the latter. p21 did not show any predictive value of DFS (p < 0.7). Neither p27 nor p21 did predict disease-specific survival (DSS) in Kaplan-Meier analysis, but DSS time was much shorter for p27-positive tumors. In multivariate (Cox) model, p27 lost its value as independent predictor of DFS, and none of the covariates were independent predictors of DSS.
  
  
  CONCLUSIONS
  p27 expression seems to be more powerful than p21 expression in providing useful prognostic information in CRC, particularly in predicting the patients at high risk for recurrent disease. Larger cohort and longer follow-up are needed to fully elucidate the value of p27 (and p21) as independent predictors of disease outcome.
authors.affiliation: Department of Pathology, King Abdul-Aziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia. jalmaghrabi@hotmail.com
authors.forename: Jaudah
authors.initials: J
authors.lastname: Al-Maghrabi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Ahwal
authors.forename: Abdelbaset
authors.initials: A
authors.lastname: Buhmeida
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Sibyani
authors.forename: Eman
authors.initials: E
authors.lastname: Emam
authors.forename: Ayman
authors.initials: A
authors.lastname: Ghanim
authors.forename: Mohmmad
authors.initials: M
authors.lastname: Al-Qahtani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27