title: p27(kipl) protein expression: an independent prognostic factor in rectal carcinoma stages I-III.
abstract: OBJECTIVE
  To evaluate the impact of some molecular markers on lymph node metastases, overall (OS) and disease-free survival (DFS) in rectal cancer.
  
  
  METHODS
  We investigated p27(kip1) , p53, nm23, and vascular endothelial growth factor (VEGF) expression in 109 primary rectal cancer specimens (stage I, n=38; stage II, n=24; stage III, n=20; and stage IV, n=27) from patients operated on between 1990 and 1995 at Clinica Chirurgica II.
  
  
  RESULTS
  Tumour differentiation (P=0.0469), depth of rectal wall invasion (T status) (P=0.0000), distant metastases (P=0.0000), vascular invasion (P=0.0000), and p27(kip1) expression (P=0.0022) were associated with lymph node metastases (N status). During follow up (median duration 47 months), 48 patients died, and 25 patients (stages I-III) had recurrences. At multivariate analysis, T and N status, and intratumoural necrosis were independent risk factors for OS. The relative risk (RR) of death for patients with lymph node metastases, advanced T status and intratumoural necrosis was 3.3 (P=0.0002), 2.03 (P=0.0127), and 1.47 (P=0.1935), respectively. When analysis included only stage I-III patients, N status and p27(kip1) protein expression were found to be independent risk factors for OS. The RR of death for patients with lymph node metastases and those without p27(kip1) expression was 2.98 (P=0.0251), and 3.57 (P=0.0231), respectively. At multivariate analysis, N status, p27(kip1) expression, and intratumoural necrosis were independent risk factors for DFS. The RR of recurrence for patients with lymph node metastases, intratumoural necrosis and absence of p27(kip1) expression was 6.29 (P=0.0001), 3.04 (P=0.0168), and 3.25 (P=0.0387), respectively.
  
  
  CONCLUSIONS
  Absence of p27(kip1) expression is a useful marker of tumour aggressiveness in rectal carcinoma stages I-III, and an independent predictor for OS and DFS.
authors.affiliation: Sezione di Clinica Chirurgica II, Dipartimento di Scienze Oncologiche e Chirurgiche, University of Padova, Padova, Italy, Sezione di Oncologia, Dipartimento di Scienze Oncologiche e Chirurgiche, University of Padova, Padova, Italy, Sezione di Anatomia Patologica, Dipartimento di Scienze Oncologiche e Chirurgiche, University of Padova, Padova, Italy.
authors.lastname: Pucciarelli
authors.lastname: Esposito
authors.lastname: Fassina
authors.lastname: Alaggio
authors.lastname: Masin
authors.lastname: Toppan
authors.lastname: Chieco-Bianchi
authors.lastname: Lise