Tumor suppressor gene alterations in malignant gliomas: Histopathological associations and prognostic evaluation

We have examined a series of 135 gliomas for alterations of the p53, CDKN2A (p16) and PTEN tumor suppressor genes (TSGs) in order to evaluate the inci dence of their inactivation as a function of tumor malignancy and cellular differentiation, and to examine potential associations with patient outcome . The composition of this series, classified using WHO criteria, is as foll ows: 27 grade 2 tumors (II astrocytomas, 12 oligoastrocytomas, 4 oligodendr ogliomas), 42 grade 3 tumors (22 astrocytomas, 16 oligoastrocytomas, 4 olig odendrogliomas), and 66 grade 4 tumors (63 astrocytomas and 3 oligoastrocyt omas). Similar frequencies of p53 mutation were observed among grade 2 (37. 0%), and grade 3 tumors (38.1%), as well as between astrocytomas and mixed tumors. CDKN2A and PTEN mutations were clearly associated with increasing t umor malignancy (occurring in 0% of grade 2 tumors, 14.3% and 4.8% respecti vely of grade 3 tumors, and 27.3% and 30.3% respectively of grade 4 tumors) and were observed at substantially higher rates among astrocytomas. For th e tumor suppressor genes examined, there was no relationship between the oc currence of any two TSG inactivation events. With regard to outcome, the p5 3 genetic status showed no significant relationship with patient survival. The CDKN2A and PTEN alterations were negative prognostic indicators of surv ival when evaluated in all 135 gliomas, but failed to predict outcome when evaluated in either of the high grade (3 or 4) tumor groups.