Immunocytochemical detection of members of the caspase cascade of apoptosis in childhood medulloblastomas.
During the process of programmed cell death (PCD), the cell disintegrates into small, membrane-bound apoptotic bodies. Caspase-3 is ubiquitously expressed in normal and neoplastically-transformed human cells and serves as an executioner in the apoptotic or PCD pathway. During our immunocytochemical study, a sensitive, four-step, alkaline phosphatase-conjugated antigen detection technique was employed. The results demonstrated the presence of apoptotic activity within the cellular microenvironment of childhood medulloblastoma/primitive neuroectodermal tumor. The observations identified the cytoplasmic presence of caspase-3 in more than 20% of neoplastic cells. The immunocytochemical expression pattern demonstrated a translocation tendency from the cytoplasm to the cell nuclei in the apoptotic cells in about 5% of the tumor cells. Caspase-3 presence was also detected in the tumor infiltrating lymphocytes (TILs), representing the host's immune, mostly CD8+, cytotoxic, tumor-associated antigen (TAA)-directed effector cells. This phenomenon may play an important role in these tumors' maintenance of immune privilege and evasion of immune attacks. We suggest that the grade and intensity of apoptosis may not only have diagnostic and prognostic significance, but could also play a leading role in the biological (fourth modality) antineoplastic treatment of these highly malignant, neuroectodermal brain tumors.
Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA. Bodey18@aol.com
Bela
B
Bodey
Stuart E
SE
Siegel
Hans E
HE
Kaiser
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D020169:Caspases / Q000032:analysis / Q000378:metabolism*; D002452:Cell Count; D002528:Cerebellar Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D007223:Infant; D016246:Lymphocytes, Tumor-Infiltrating / Q000201:enzymology / Q000473:pathology; D008527:Medulloblastoma / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology
D014408:Biomarkers, Tumor; D020169:Caspases