CLINICAL AND PROGNOSTIC-SIGNIFICANCE OF KI-67 AND PROLIFERATING CELL NUCLEAR ANTIGEN EXPRESSION IN CHILDHOOD PRIMITIVE NEUROECTODERMAL BRAIN-TUMORS

The cell proliferation activity of sixteen childhood primitive neuroec todermal tumors (PNETs) was observed immunocytochemically, to determin e the cell kinetics and cell proliferation activity of these relativel y undifferentiated, malignant brain tumors. Two mouse anti-human monoc lonal antibodies (MoABs) were employed for the detection of the nuclea r antigens (Ki-67) present during proliferation in frozen sections and proliferating cell nuclear antigen (PCNA) expression in formalin fixe d, paraffin embedded tissue sections. A sensitive four step, indirect, streptavidin-biotin, alkaline phosphatase (AP) conjugated, immunocyto chemical experimental technique, was used. The nuclear anti-Ki-67 MoAB which binds to a special nuclear antigen, identified its expression o nly in proliferating cells. This nuclear antigen was detectable during the whole mitotic cycle of all malignant and fast proliferating cells , only absent between and during phases G(0) (resting phase) and the f irst gap phase (G(1)). The mean labelling index (MLI) was defined as t he percentage of Ki-67 and PCNA antigen positive cells of the total nu mber counted. The MLI for the PNETs ranged between 1.4% and 11.6%, wit h a mean MLI of 6.2% for Ki-67; and between 3.2% and 16.8% with a mean of 9.74% for PCNA. All observed PNETs demonstrated heterogeneous nucl ear stainings, but the highest MLIs were found among the poorly differ entiated classic medulloblastomas (over 30% for the Ki-67 antigen and 46% for PCNA). MLIs were low in 5/13 PNETs (under 4% for antigen Ki-67 and 9.4% for PCNA) and in this group we defined our lowest (1.4%) MLI , suggesting the presence of in vivo neuritogens of these undifferenti ated, embryonal tumors. MLIs in 6/13 PNETs were intermediated in magni tude. The MLIs were higher in two PNETs with clear cellular differenti ation towards an ependymal (10.4%) and melanocytic (8.8%) direction. F ormation of astrocytes within the tumor mass did not affect the interm ediate character of the MLI (7.8%). The prognosis of every interactive tumor is obviously correlated with its proliferation activity and cel l kinetics. The clinical significance of these parameters is great sin ce they provide direct information concerning the growth characteristi cs of an intracranial tumor.