Comparison of Cyclin A and MIB-1 Expression in Astrocytic Tumors Using Image-Based Cell Analysis System

Abstract

Traditional prognostic indicators for astrocytic tumors include tumor size, type, and histologic grade. Data suggest that tumor growth fraction assessed by MIB-1 is an important predicator of survival. Cyclin A, like MIB-1, is a recently described specific marker of proliferation, detectable primarily in S phase of the cell cycle as it undergoes progression to G2 phase. Thirty-seven cases of astrocytic tumors--14 cases of World Health Organization grade 1 and 2 (low grade tumors), 8 cases of grade 3 (anaplastic astrocytoma), and 15 cases of grade 4 (glioblastoma multiforme)--were simultaneously evaluated using routine paraffin immunohistochemical methods with commercial antibodies against MIB-1 and cyclin A. The results were quantitated using a Cell Analysis System (CAS) 200 image analyzer. The mean percentage positive nuclear area for MIB-1 was 3.32% in grade 1 and 2, 19.27% in grade 3, and 24.00% in grade 4 astrocytic tumors. Cyclin A showed a similar pattern of positivity in the same cases: 2.84% in grade 1 and 2, 16.27% in grade 3, and 24.88% in grade 4 astrocytic tumors. The data suggest that both proliferation markers correlated significantly with histologic grade. Cyclin A appears to be as good an indicator of brain tumor proliferation as MIB-1. Because cyclin A is detectable primarily in the S phase of the cell cycle, the fraction of cells positive for cyclin A should allow for a more accurate indicator of tumor progression.