Article
Lab Invest 2001, 81:681–688
Caspase-3 Activity as a Prognostic Factor in Colorectal Carcinoma
Liesbeth E Jonges1,2, J Fred Nagelkerke4, N Geeske Ensink2, Edo A van der Velde3, Rob A E M Tollenaar2, Gert Jan Fleuren1, Cornelis J H van de Velde2, Hans Morreau1 and Peter J K Kuppen2
- 1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
- 2Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
- 3Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
- 4Department of Toxicology, Leiden Amsterdam Center for Drugs Research, Leiden, The Netherlands
Correspondence: Dr. Peter J. K. Kuppen, Leiden University Medical Center, Surgery Oncology-Laboratory for Immunotherapy, LO-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: kuppen@lumc.nl
Received 22 November 2000.
Abstract
Several techniques to determine apoptotic frequencies in tumors have been described. In this study, we report that biochemical detection of enzymatic caspase-3 activity is a simple and quantitative technique to measure apoptosis in colorectal tumor cells. The relevance of the level of apoptosis in colorectal cancer for the clinical course remains unclear. Therefore, we studied the correlation between caspase-3 activity and prognosis of the disease in relation to different factors known to be involved in apoptosis induction. High caspase-3 activity significantly correlated with a higher risk of recurrence and was preferentially found in tumors of the right side of the colon. No correlation was detected between high caspase-3 activity and altered protein expression of p53,
-catenin, or proteins of mismatched repair genes. This indicates that high caspase-3 activity has no evident correlation with the genetic Wnt-signaling or the mismatch repair mutational pathways. The caspase-3 activity significantly correlated with CD57+ tumor infiltrating cells. Therefore, high caspase-3 activity in right-sided tumors might be induced by a specific lymphocytic reaction.

