Determining diagnosis, assessing prognosis, and assigning appropriate therapy for patients with gliomas has traditionally relied on pathological and clinical factors. These factors include the age, sex, and performance status as well as tumor histologic type, pathologic grade, and specific location. Some of these factors are easy to assess while others, especially histologic type and grade, can be difficult and depend upon the interpretation of a skilled neuropathologist. Molecular genetic, cytogenetic, flow cytometric, and immunohistochemical factors have been used to assess many solid tumors including gliomas. During the initial grant period at Mayo several potential factors which may be useful in the classification of glial tumors have been identified The first goal of the next study period is: to determine if such factor can be used to classify astrocytic tumors of favorable and poor prognosis. The second goal is to develop markers which will reliably differentiate astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. Several groups of tumor specimens will be available to help achieve these goals: 1) the set of frozen gliomas prospectively obtained at Mayo during the initial and renewal project period, 2) sets of paraffin-embedded gliomas from patients entered on previous and current prospective clinical trials of the North Central Cancer Treatment Group (NCCTG) and the Radiation Therapy Oncology Group (RTOG), and 3) a large series of retrospectively ascertained paraffin-embedded gliomas previously treated at Mayo but not part of the preceding two groups.
The specific aims of this project are to: 1) to evaluate the diagnostic and prognostic relevance of alterations of specific chromosomes and chromosomal regions detected by polymerase chain reaction (PCR) analysis of microsatellite repeats and fluorescent in situ hybridization (FISH). 2) To evaluate the diagnostic and prognostic relevance of DNA ploidy by flow cytometric analysis and to compare this analysis with ploidy determination by FISH. 3) To assess the diagnostic and prognostic relevance of various markers of cellular proliferation and cellular function including flow cytometric determination of %S-phase, %G2M, and immunohistochemical evaluation of PCNA, Ki67, and p53. 4) To evaluate molecular markers proposed by the other institutions supported by this cooperative agreement and to share techniques, tissues, and expertise with these institutions. The long-term objective of this project is to assess and utilize molecular markers to more accurately classify and grade gliomas and thus improve the prediction of prognosis and the assignment of optimal therap for patients with these tumors.
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