Prognostic value of the expression of tumor suppressor genes p53, p21, p16and pRb, and Ki-67 labelling in high grade astrocytomas treated with radiotherapy

Cumulative inactivation of tumor suppressor genes and/or amplification of o ncogenes lead to progressively more malignant astrocytic tumors. We have an alyzed the significance of tumor suppressor genes p53, p21, p16 and retinob lastoma protein (pRb) and proliferative activity for survival in 77 high gr ade astrocytic tumors. After operation, the patients - 25 anaplastic astrocytomas (AA) and 52 glio blastomas (GBs) - were treated with similar radiotherapy. The expression of the suppressor genes and the proliferative activity were analyzed immunohi stochemically. p53 immunopositivity was found in 44% of AAs and 46% of GBs. Tumors with ab errant p53 expression had lower proliferation indices than p53 immunonegati ve tumors. Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival, p16 immunostaining was negative in 16 % of AAs and in 44% of GBs, and it correlated inversely with survival in bo th uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusi ve. Ki-67 labelling index (LI) was significantly higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20% and this subset of AAs had similar prognosis as GB. In high grade astrocytic tumors p16 immunonegativity was an independent ind icator of poor prognosis in addition to the previously established patient' s age, histopathology and Ki-67 LI. Furthermore, there was a subset of AAs with a high proliferation rate (> 20%) in which the histopathological hallm arks of GB were lacking, but which had similarly dismal prognosis as GB.