Immunocytochemical mapping of the phosphatase and tensin homolog (PTEN/MMAC1) tumor suppressor protein in human gliomas

PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multiple advanced can cers 1) is a tumor suppressor gene, the inactivation of which is an importa nt step in the progression of gliomas to end-stage glioblastoma multiforme. We examined the distribution of PTEN protein in 49 primary human gliomas b y immunocytochemistry using polyclonal antibodies that we raised against PT EN-glutathione S-transferase fusion proteins expressed in Escherichia coli. The study group consisted of 6 low-grade astrocytomas, 7 anaplastic astroc ytomas, 21 glioblastomas multiforme, 4 low-grade oligodendrogliomas, 6 mali gnant oligodendrogliomas, and 5 malignant mixed oligoastrocytomas. For each tumor, we determined the percentage of tumor cells showing PTEN immunoreac tivity in the most cellular regions of the tumor specimen. In both astrocyt omas and oligodendrogliomas, there was an inverse relationship between the percentage of PTEN+ cells and malignancy grade, consistent with a role for PTEN as a tumor suppressor gene, the expression of which declines during gl ioma progression. In nonneoplastic tissue, PTEN was expressed in human feta l brain at 61G, 23, and 27 weeks' gestation, but not in adult brain, indica ting that PTEN is developmentally regulated in the CNS. In 21 glioblastomas multiforme, we correlated PTEN protein expression with PTEN gene sequence. Although PTEN-mutant tumors showed significantly diminished PTEN protein e xpression compared with wild-type cases, suppressed expression of PTEN is m ore prevalent than predicted from mutation frequencies.