Caspase-3 activity as a prognostic factor in colorectal carcinoma.
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, beta-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.
Jonges
L E
LE
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Nagelkerke
J F
JF
Ensink
N G
NG
van der Velde
E A
EA
Tollenaar
R A
RA
Fleuren
G J
GJ
van de Velde
C J
CJ
Morreau
H
H
Kuppen
P J
PJ
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018959:CD57 Antigens / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009364:Neoplasm Recurrence, Local / Q000201:enzymology; D011379:Prognosis; D012307:Risk Factors
D014408:Biomarkers, Tumor; D018959:CD57 Antigens; D017493:Leukocyte Common Antigens; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases