Prognostic significance of p27(kip-1) expression in colorectal adenocarcinomas is associated with tumor stage.
OBJECTIVE
Although the decreased expression of p27(kip-1), a cyclin-dependent kinase inhibitor, has been correlated with advanced tumor stage and short survival of patients with colorectal adenocarcinomas (CRCs), its prognostic value based on the tumor site, tumor stage, and patient ethnicity was not assessed. Therefore, in this study, we investigated whether the prognostic value of p27(kip-1) expression varies with the tumor site, tumor stage and patient ethnicity.


METHODS
We evaluated 206 (85 African Americans and 121 Caucasians) archival tissue specimens of first primary CRCs for immunohistochemical expression of p27(kip-1), and its prognostic significance was analyzed using univariate Kaplan-Meier and multivariate Cox regression survival methods.


RESULTS
Although, similar proportion of CRCs with decreased p27(kip-1) expression was observed in all stages (range, 26-36%), the decreased p27(kip-1) expression has been shown as a marker of poor prognosis only for patients with stage III tumors both in univariate (log-rank test, P = 0.014) and multivariate (hazard ratio = 3.2, 95% confidence interval = 1.3-7.7; P = 0.01) survival analyses. The decreased expression of p27(kip-1) was associated with a high histologic grade (P = 0.016) in stage II CRCs, and with distal tumors (P = 0.001), tumor invasion (P = 0.044), and with local recurrence (P = 0.008) in stage III CRCs.


CONCLUSIONS
No prognostic significance was found for p27(kip-1) expression in stages I, II, or IV CRCs, and its prognostic value was not associated with either ethnicity or tumor location. These studies suggest that decreased expression of p27(kip-1) is an indicator of poor prognosis and aids in identifying a subset of patients with aggressive forms of stage III CRCs.
Manne
Upender
U
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA. manne@path.uab.edu
Jhala
Nirag C
NC
Jones
Jennifer
J
Weiss
Heidi L
HL
Chatla
Chakrapani
C
Meleth
Sreelatha
S
Suarez-Cuervo
Catalina
C
Grizzle
William E
WE
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D044469:Racial Groups; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27