Absence of the cell cycle inhibitor p27Kip1 protein predicts poor outcome in patients with stage I-III colorectal cancer.
BACKGROUND
The p27Kip1 protein regulates the G1 to S phase transition of cell cycle by binding to and inhibiting the cyclin E/Cdk2 complex. This study explores the prognostic significance of the absence of the p27Kip1 protein in patients with colorectal cancer (CRC).


METHODS
Formalin-fixed tumor sections from 124 patients who underwent curative resection for stage I-III CRC were analyzed by immunohistochemistry using MoAb anti-p27KiP1.


RESULTS
Detectable levels of p27Kip1 protein were found in 86% of tumors. Median follow-up was 55 months. Actuarial 5-year disease-free survival (DFS) and overall survival (OS) were 76% and 85%, respectively, in patients with tumors with p27Kip1 protein expression and 34% and 40%, respectively, in those whose tumors lacked p27Kip1 protein expression (P < .001). At multivariate analysis, tumor stage (III vs. I-II) and p27Kip1 protein status (absence vs. presence) were found to be independent prognostic factors for DFS and OS.


CONCLUSIONS
Lack of p27KiP1 protein expression in CRC is a negative prognostic marker and may therefore be useful in selecting early-stage patients more likely to benefit from adjuvant treatment.
Belluco
C
C
Department of Oncological Sciences, University of Padova, Italy.
Esposito
G
G
Bertorelle
R
R
Del Mistro
A
A
Fassina
A
A
Vieceli
G
G
Chieco-Bianchi
L
L
Nitti
D
D
Lise
M
M
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases