Cell cycle regulators (p21, p53, pRb) in oligodendrocytic tumors: A study by novel tumor microarray technique

Using the novel tissue microarray technique, we studied immunohistochemical expression of cell cycle regulators p53, p21, pRb in 42 grade II oligodend rogliomas, 16 grade III anaplastic oligodendrogliomas, 10 primary and 4 rec idive grade II oligoastrocytomas, 10 grade III oligoastrocytomas and 2 othe r grade II mixed gliomas. The p53 immunopositivity associated with malignan t histology of the tumor (p = 0.01, Mann-Whitney test) and high pRb express ion (p = 0.015). The p21 score associated strongly with histological grade (p < 0.001). The immunopositive tumors had a significantly higher rate of p roliferation (p = 0.021). The p21 immunopositivity correlated positively wi th p53 immunopositivity: among the 33 p21 immunopositive tumors 30 (91%) we re p53 immunopositive and only 3 were p53 immunonegative (p = 0.017). Patie nts with p21 immunonegative primary tumors had significantly better prognos is: among them 42 of the 46 (91%) survived, whereas only 18 of the 30 patie nts (60%) with p21 immunopositive primary tumors survived until the follow- up date (p = 0.0017). Statistical significance was reached in multivariate analysis as well (p = 0.01, exp(B) = 5.5). The pRb immunopositive tumors ha d higher proliferation rate than immunonegative tumors (p = 0.002). In mult ivariate variance analysis, comparing the effects of different regulatory p roteins on cell proliferation, only the amount of pRb expression reached st atistical significance (p = 0.004). In conclusion, the expression of p21 in oligodendrocytic tumors seems to be upregulated by p53 expression which ri ses with cell proliferation and malignancy as in attempt to halt cell cycle but seems to be overrun by other factors. The amount of p21 expression has independent prognostic significance and could be used in diagnosis to help the difficult evaluation of the malignancy potential of oligodendrogliomas and oligoastrocytomas.