Spindle checkpoint protein hMad2 and histone H3 phosphoserine 10 mitosis marker in pediatric solid tumors.
Pediatric solid tumors of different histologic types are often treated with drugs (such as vincristine) that directly or indirectly target the mitotic spindle and the spindle checkpoint, leading to mitotic arrest, mitotic catastrophe and apoptosis. hMad2 (mitosis arrest deficient 2) expression in neuroblastoma has suggested utility in predicting prognosis. The present study was undertaken to determine hMad2 expression patterns in pediatric solid tumors, and its relationship to overall treatment response and short-term survival (2-years). The expression of hMad2 and histone H3-serine 10 phosphoprotein (mitosis marker) were examined using immunohistochemical staining methods in 26 pediatric solid tumors (six neuroblastomas, eight Wilm's, five sarcomas, four lymphomas and three hepatoblastomas). hMad2 expression paralleled overall histone H3 phosphoserine 10 expression in most tumor types. Low hMad2 score tumors (0-3.5) exhibited lower complete response (66.67%) and a higher recurrence/progressive disease (33.33%) than high score tumors (4-6) (78.57% and 21.43. %), consistent with predicted hMad2 function and reports in adult tumors. Histone H3 serine 10 phosphoprotein is useful in mitosis enumeration and hMad2 expression may provide additional help in neuroblastoma profiling and could be useful when spindle checkpoint specific target drugs are used.
Idikio
Halliday A
HA
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. hidikio@ualberta.ca
D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002648:Child; D018197:Hepatoblastoma / Q000378:metabolism; D006657:Histones / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000378:metabolism; D064246:Mad2 Proteins; D008938:Mitosis / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009447:Neuroblastoma / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis*; D012509:Sarcoma / Q000378:metabolism; D009396:Wilms Tumor / Q000378:metabolism
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D006657:Histones; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D010768:Phosphoserine