The first goal of this project is to systematically evaluate the impact of our initial data that MIB-1 labeling indices (LI) of focal regions of proliferation in grade Il astrocytomas predict patient survival. Patients with this neoplasm have a wide range of survivals despite the same histopathologic features of their tumors, confounding prediction of outcome by the neuropathologist. MIB- l is a new genetically engineered marker of cellular proliferation that recognizes Ki-67 epitopes in paraffin sections of archival tissue. In a recent study of grade Il astrocytomas, sampling focal regions of highest proliferation labeled by MIB-1 in each astrocytoma maximized its predictive power. We will evaluate whether this predictive value of MIB- l discovered at the University of Michigan Medical Center is relevant to other groups of grade Il astrocytoma patients from different racial backgrounds and hospital environment. This evaluation will be enhanced by collaborations with other institutions, and by new collaborations with cooperative cancer study groups. The predictive power of MIB- l LI will be compared with other clinical and prognostic factors including age, gender, symptoms, and treatments. The effects on predictive capabilities of these factors including MIB- l of recent change in World Health Organization (WHO) classification systems will be accessed. Although their average survival is less than grade Il astrocytoma patients grade III anaplastic astrocytoma patients have a wide range of outcomes. Our second goal will be to evaluate the predictive power of MIB- l to differentiate long and short survivors in this single histopathologic category. The analytical approach and strategy to pursue positive results will be the same as described above. Finally, the effects of sampling on histopathologic grading and on MIB-l LI will be assessed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA068545-02
Application #
2748816
Study Section
Special Emphasis Panel (ZRG2-MEP (04))
Program Officer
Jacobson, James W
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Xin, Wei; Rubin, Mark A; McKeever, Paul E (2002) Differential expression of cytokeratins 8 and 20 distinguishes craniopharyngioma from rathke cleft cyst. Arch Pathol Lab Med 126:1174-8
Arteaga, C L; Chinratanalab, W; Carter, M B (2001) Inhibitors of HER2/neu (erbB-2) signal transduction. Semin Oncol 28:30-5
Busse, D; Yakes, F M; Lenferink, A E et al. (2001) Tyrosine kinase inhibitors: rationale, mechanisms of action, and implications for drug resistance. Semin Oncol 28:47-55
McKeever, P E; Junck, L; Strawderman, M S et al. (2001) Proliferation index is related to patient age in glioblastoma. Neurology 56:1216-8
Vortmeyer, A O; Huang, S C; Koch, C A et al. (2000) Somatic von Hippel-Lindau gene mutations detected in sporadic endolymphatic sac tumors. Cancer Res 60:5963-5
Busse, D; Doughty, R S; Arteaga, C L (2000) HER-2/neu (erbB-2) and the cell cycle. Semin Oncol 27:3-8; discussion 92-100
McKeever, P E (1998) Insights about brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers. J Histochem Cytochem 46:585-94
McKeever, P E; Strawderman, M S; Yamini, B et al. (1998) MIB-1 proliferation index predicts survival among patients with grade II astrocytoma. J Neuropathol Exp Neurol 57:931-6