© 2000 by Society
© 2000 by the Society forNeuro-Oncology
Immunocytochemical mapping of the phosphatase and tensin homolog(PTEN/MMAC1) tumor suppressor protein in human gliomas
Department of Neurosurgery and Huntsman Cancer Institute, Universityof Utah Health Sciences Center, Salt Lake City, UT 84132
2 Address correspondence and reprint requests to Dan Fults, Department ofNeurosurgery, University of Utah Health Sciences Center, Salt Lake City, UT84132.
PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multipleadvanced cancers 1) is a tumor suppressor gene, the inactivation of which isan important step in the progression of gliomas to end-stage glioblastomamultiforme. We examined the distribution of PTEN protein in 49 primary humangliomas by immunocytochemistry using polyclonal antibodies that we raisedagainst PTEN-glutathione S-transferase fusion proteins expressed inEscherichia coli. The study group consisted of 6 low-gradeastrocytomas, 7 anaplastic astrocytomas, 21 glioblastomas multiforme, 4low-grade oligodendrogliomas, 6 malignant oligodendrogliomas, and 5 malignantmixed oligoastrocytomas. For each tumor, we determined the percentage of tumorcells showing PTEN immunoreactivity in the most cellular regions of the tumorspecimen. In both astrocytomas and oligodendrogliomas, there was an inverserelationship between the percentage of PTEN+ cells and malignancygrade, consistent with a role for PTEN as a tumor suppressor gene,the expression of which declines during glioma progression. In nonneoplastictissue, PTEN was expressed in human fetal brain at 16, 23, and 27 weeks'gestation, but not in adult brain, indicating that PTEN is developmentallyregulated in the CNS. In 21 glioblastomas multiforme, we correlated PTENprotein expression with PTEN gene sequence. AlthoughPTEN-mutant tumors showed significantly diminished PTEN proteinexpression compared with wild-type cases, suppressed expression of PTEN ismore prevalent than predicted from mutation frequencies.
Received June 25, 1999; Accepted October 29, 1999
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