Immunohistochemical expression of caspase-3 as an adverse indicator of the clinical outcome in human breast cancer.
OBJECTIVE
Tumor growth is the net result of cell proliferation and cell loss by apoptosis. Caspase-3 (CPP32) has been considered as most directly correlated with apoptosis because of its location in the protease cascade pathway. The aim of this study was to examine the relation of the immunohistochemical expression of caspase-3 in 137 infiltrating breast carcinomas to patients' clinicopathological parameters and survival.


METHODS
A polyclonal antibody against caspase-3 was applied using a standard immunohistochemical procedure to paraffin sections.


RESULTS
By comparison with nonneoplastic breast tissue, caspase-3 appeared to be upregulated in malignant breast tissue, and its overexpression status was detected in 75.2% of the specimens. Significant statistical correlations were observed between overexpression of caspase-3 and low nuclear grade (p = 0.048), lack of p53 protein accumulation (p = 0.039), bcl-2-positive immunostaining (p = 0.027), as well as tissue inhibitor of metalloproteinase-2 immunoreactivity of neoplastic (p = 0.012) and stromal cells (p = 0.0001). Despite the above correlations, multivariate analysis revealed a significant negative influence of caspase-3 expression on patients' overall survival (p = 0.029).


CONCLUSIONS
Caspase-3 protein overexpression appears to be involved in the apoptotic pathways influenced by wild-type p53 and bcl-2 proteins. Moreover, the results show that caspase-3 overexpression in breast cancer cells seems to exert an independent adverse effect on patients' overall survival.
Nakopoulou
L
L
Department of Pathology, School of Medicine, National and Capodistrian University of Athens, Greece. lnakopou@cc.uoa.gr
Alexandrou
P
P
Stefanaki
K
K
Panayotopoulou
E
E
Lazaris
A C
AC
Davaris
P S
PS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000201:enzymology / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D053148:Caspase 3; D020169:Caspases / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019716:Tissue Inhibitor of Metalloproteinase-2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases