Caspase-3 activity predicts local recurrence in rectal cancer.
Publication year
2007Source
Clinical Cancer Research, 13, 19, (2007), pp. 5810-5ISSN
Publication type
Article / Letter to editor
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Organization
Pathology
Journal title
Clinical Cancer Research
Volume
vol. 13
Issue
iss. 19
Page start
p. 5810
Page end
p. 5
Subject
NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 2: Age-related aspects of cancer; ONCOL 3: Translational research; UMCN 1.2: Molecular diagnosis, prognosis and monitoringAbstract
PURPOSE: Radiotherapy followed by total mesorectal excision surgery has been shown to significantly reduce local recurrence rates in rectal cancer patients. Radiotherapy, however, is associated with considerable morbidity. The present study evaluated the use of biochemical detection of enzymatic caspase-3 activity as preoperative marker for apoptosis to preselect patients that are unlikely to develop a local recurrence to spare these patients from overtreatment and the negative side effects of radiotherapy. EXPERIMENTAL DESIGN: Nonirradiated freshly frozen tissue samples from 117 stage III rectal cancer patients were collected from a randomized clinical trial that evaluated preoperative radiotherapy in total mesorectal excision surgery. Additional frozen archival tissues from 47 preoperative biopsies and corresponding resected colorectal tumors were collected. Level of apoptosis was determined by measuring the enzymatic activity of caspase-3 in a biochemical assay. RESULTS: In tumor tissue, caspase-3 activity lower than the median was predictive of 5-year local recurrence (hazard ratio, 7.4; 95% confidence interval, 1.7-32.8; P = 0.008), which was unaffected by adjustment for type of resection, tumor location, and T status (adjusted hazard ratio, 7.5; 95% confidence interval, 1.7-34.1; P = 0.009). Caspase-3 activity in preoperative biopsies was significantly correlated with caspase-3 activity in corresponding resected tumors (r = 0.56; P < 0.0001). CONCLUSION: Detection of tumor apoptosis levels by measuring caspase-3 activity, for which a preoperative biopsy can be used, accurately predicted local recurrence in rectal cancer patients. These findings indicate that caspase-3 activity is an important denominator of local recurrence and should be evaluated prospectively to be added to the criteria to select rectal cancer patients in which radiotherapy is redundant.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122537]
- Faculty of Medical Sciences [90372]
- Open Access publications [97529]
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