Abstract
Background and aims
The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy.
Materials and methods
We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] > 5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed.
Results
Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p = 0.001), showing a statistically significant correlation (r = 0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR = 3.53 [1.13–10.90], p = 0.02), age (OR = 1.09 [1.01–1.18], p = 0.03), Dukes stage (OR = 1.93 [1.01–3.70]), caspase-3 activity in normal mucosa (OR = 1.02 [1.01–1.04], p = 0.017) and caspase-3 activity in tumour (OR = 1.02 [1.01–1.03], p = 0.013).
Conclusion
Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.
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This work was supported by the Spanish government through project FISS 01/1260.
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de Oca, J., Azuara, D., Sanchez-Santos, R. et al. Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer. Int J Colorectal Dis 23, 21–27 (2008). https://doi.org/10.1007/s00384-007-0362-3
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DOI: https://doi.org/10.1007/s00384-007-0362-3