319 335

Cited 83 times in

Analysis of Apoptosis Protein Expression in Early-Stage Colorectal Cancer Suggests Opportunities for New Prognostic Biomarkers

Authors
 Maryla Krajewska  ;  Hoguen Kim  ;  Chul Kim  ;  Haeyoun Kang  ;  Kate Welsh  ;  Shu-ichi Matsuzawa  ;  Michelle Tsukamoto  ;  Ronald G. Thomas  ;  Nuria Assa-Munt  ;  Zhe Piao  ;  Koichi Suzuki  ;  Manuel Perucho  ;  Stan Krajewski  ;  John C. Reed 
Citation
 CLINICAL CANCER RESEARCH, Vol.11(15) : 5451-5461, 2005 
Journal Title
CLINICAL CANCER RESEARCH
ISSN
 1078-0432 
Issue Date
2005
MeSH
Age Factors ; Apoptosis* ; Apoptotic Protease-Activating Factor 1 ; Biomarkers/metabolism ; Biomarkers, Tumor/metabolism* ; Chemotherapy, Adjuvant ; Colonic Neoplasms/pathology ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/metabolism* ; Colorectal Neoplasms/pathology* ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Microsatellite Repeats ; Multivariate Analysis ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Prognosis ; Proportional Hazards Models ; Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Retrospective Studies ; Sex Factors ; Time Factors ; Tissue Distribution ; Treatment Outcome
Keywords
16061861
Abstract
PURPOSE: Although most stage II colon cancers are potentially curable by surgery alone, approximately 20% of patients relapse, suggesting a need for establishing prognostic markers that can identify patients who may benefit from adjuvant chemotherapy. We tested the hypothesis that differences in expression of apoptosis-regulating proteins account for differences in clinical outcome among patients with early-stage colorectal cancer.
EXPERIMENTAL DESIGN: Tissue microarray technology was employed to assay the expression of apoptosis-regulating proteins by immunohistochemistry in 106 archival stage II colorectal cancers, making correlations with disease-specific survival. The influence of microsatellite instability (MSI), tumor location (left versus right side), patient age, and gender was also examined.
RESULTS: Elevated expression of several apoptosis regulators significantly correlated with either shorter (cIAP2; TUCAN) or longer (Apaf1; Bcl-2) overall survival in univariate and multivariate analyses. These biomarkers retained prognostic significance when adjusting for MSI, tumor location, patient age, and gender. Moreover, certain combinations of apoptosis biomarkers were highly predictive of death risk from cancer. For example, 97% of patients with favorable tumor phenotype of cIAP2(low) plus TUCAN(low) were alive at 5 years compared with 60% of other patients (P = 0.00003). In contrast, only 37% of patients with adverse biomarkers (Apaf1(low) plus TUCAN(high)) survived compared with 83% of others at 5 years after diagnosis (P< 0.0001).
CONCLUSIONS: Immunohistochemical assays directed at detection of certain combinations of apoptosis proteins may provide prognostic information for patients with early-stage colorectal cancer, and therefore could help to identify patients who might benefit from adjuvant chemotherapy or who should be spared it.
Files in This Item:
T200500987.pdf Download
DOI
10.1158/1078-0432.CCR-05-0094
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hogeun(김호근)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151166
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links