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Cathepsin B expression and survival in colon cancer: implications for molecular detection of neoplasia.

Authors :
Chan AT
Baba Y
Shima K
Nosho K
Chung DC
Hung KE
Mahmood U
Madden K
Poss K
Ranieri A
Shue D
Kucherlapati R
Fuchs CS
Ogino S
Source :
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2010 Nov; Vol. 19 (11), pp. 2777-85. Date of Electronic Publication: 2010 Sep 10.
Publication Year :
2010

Abstract

Background and Aims: Proteases play a critical role in tumorigenesis and are upregulated in colorectal cancer and neoplastic polyps. In animal models, cathepsin B (CTSB)-activatable imaging agents show high enzyme activity within intestinal tumors.<br />Methods: We conducted a prospective cohort study of 558 men and women with colon cancer with tumors that were accessible for immunohistochemical assessment. We used Cox proportional hazards models, stratified by stage, to compute colon cancer-specific and overall mortality according to tumoral expression of CTSB.<br />Results: Among 558 participants, 457 (82%) had tumors that expressed CTSB (CTSB positive) and 101 (18%) had tumors that did not express CTSB (CTSB negative). CTSB expression was not associated with disease stage (P = 0.19). After a median follow-up of 11.6 years, there were 254 total and 155 colon cancer-specific deaths. Compared with participants with CTSB-negative tumors, participants with CTSB-positive tumors experienced a multivariate hazard ratio for colon cancer-specific mortality of 1.99 (95% confidence interval, 1.19-3.34) and overall mortality of 1.71 (95% confidence interval, 1.16-2.50). CTSB expression was independently associated with KRAS (P = 0.01) and BRAF mutation (P = 0.04), but not microsatellite instability status, CpG island methylator phenotype status, PIK3CA mutation, LINE-1 methylation, TP53 expression, or PTGS2 (cyclooxygenase-2) expression. Among 123 individuals with adenomas, 91% expressed CTSB.<br />Conclusions: As assessed by immunohistochemistry, CTSB is expressed in the vast majority of colon cancers, independent of stage, and is significantly associated with higher risk of colon cancer-specific and overall mortality.<br />Impact: These results support the potential of CTSB a target for image detection of neoplastic lesions in humans.<br /> (©2010 AACR.)

Details

Language :
English
ISSN :
1538-7755
Volume :
19
Issue :
11
Database :
MEDLINE
Journal :
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Publication Type :
Academic Journal
Accession number :
20833970
Full Text :
https://doi.org/10.1158/1055-9965.EPI-10-0529