Cyclooxygenase-2 Expression Predicts Prognosis in Astrocytic Tumors

OBJECTIVE: Cyclooxygenase-2, the inducible isoform of prostaglandin H synthesis, has been implicated in the growth and progression of a various human cancer. Although COX-2 overexpression has been observed in humangliomas, the prognostic or clinical relevance of this overexpression has rarely been investigated to date. METHODS: We examined COX-2 expression by immunohistochemistry in tumor specimens from 25 patients with low- and high grade astrocytomas and correlated the grade of COX-2 expression with patients survival. RESULTS: Immunohistochemical staining results were as follows: negative staining, N=4(16%), positive staining, N=21(84%). Results of low grade astrocytoma(N=10) were as follows: negative staining, N=3(30%), weak positivestaining, N=7(70%). Anaplastic astrocytomas(N=4) as follows: negative staining, N=1(25%), weak positivestaining, N=3(75%). Glioblastomas(N=11) as follows: negative staining, N=0(0%), weak positive staining, N=5(45%), strong positive staining, N=6(55%). As a group, tumors with higher rate of cell proliferation tended to have increased expression of COX-2. The percentage of COX-2 expression were associated with a worse survival rate(p=0.0028), and the grade of astrocytic tumors(p=0.001). These findings indicate that high COX-2 expression in tumor cell is associated with clinically more aggressive gliomas, and is a strong predictor of poor survival. CONCLUSION: Our study provides evidence that COX-2 is up-regulated in the majority of high-grade gliomas and that increased COX-2 expression is a significant negative predictor of survival and selective COX-2 inhibitors may have a potential role as an adjuvant therapy of astrocytic tumors.

Immunohistochemical Study of p53 Gene Expression in Astrocytic Neoplasms

Nineteen astrocytic neoplasms, such as 9 cases of glioblastoma multiforme, 6 cases of anaplastic astrocytoma and 4 cases of low grade astrocytoma, were analysed in view of the relationship between histopathologic grade, nuclear pleomorphism, grade of mutant p53 gene expression and mean survival time after operation. The histopathologic classification by Ringertz and immunohistochemical stain for mutant p53 gene with the DO-7 anti-p53 oncoprotein mouse monoclonal antibody were applied, and the results obtained were as follows; 1) Among 19 cases, 18 cases were located in the supratentorium, where 13 cases(42%) were located in the left and 17 cases(55%) in the right. 2) The p53 gene expression was detected in 12(63.2%) of the cases, as revealed by positive nuclear staining. All cases of glioblastoma multiforme showed p53 gene expression, compared with two(33.3%) cases of anaplastic astrocytoma and one(25%) case of low grade astrocytoma. The frequency and degree of histopathologic grade(p=0.03). 3) The mean survival time after operation was 29.49+/-4.08 months in cases with p53-negative tumors and 12.93+/-3.14 months in cases with p53-positive tumors(p<0.05). 4) Both histopathological classification and p53 gene expression showed a significant influence on servival(p=0.02 and p=0.03, respectively). 5) The relative risk for survival time was the highest in p53 gene expression. In conclusion, p53 gene expression appears to be one of the recommendable prognosticators among astrocytic neoplasms.