PROGNOSTIC-SIGNIFICANCE OF PROLIFERATIVE INDEXES IN MENINGIOMAS

The prognostic value of tumor proliferative indices in meningiomas was assessed by mitotic counts and by immunocytochemistry using a monoclonal antibody against the proliferating cell nuclear antigen (PCNA) (clone 19A2), a 36-kd nuclear protein involved in DNA synthesis. Sixty-three intracranial meningiomas were classified as benign (26), with atypical features (24) or as malignant (13). The patients included 24 men and 39 women, mean age 54.2 +/- 1.7 (mean +/- SEM) (range 15-78) at initial presentation. Twenty-four of the 63 primary tumors recurred locally, including 23.1% (6/26) of the benign, 37.5% (9/24) of the atypical, and 69.2% (9/13) of the malignant meningiomas. Among tumors that recurred, 1/9 (11%) of the atypical and 5/9 (55.5%) of the malignant tumors had had macroscopical total excision at the initial surgery. The mean interval to recurrence was 52 +/- 11.8 months. The mean progression-free follow-up period for patients without tumor recurrence was 82 +/- 8.5 months. Analysis of variance revealed that significant differences existed between tumor grades for both PCNA indices(1.16 +/- 0.29% for benign; 14.14 +/- 2.07% for atypical and 21.37 +/- 5.47% for malignant) and mitotic indices (total counts per ten high power fields) (0.08 I 0.05 for benign, 4.75 +/- 0.91 for atypical and 19.00 +/- 4.07 for malignant). Multivariate regression analysis indicated that mitotic index > 6 was the single most important factor (p < 0.05) for shorter disease-free interval. Age, sex and total surgical excision were not significant factors. PCNA index was a significant factor in the univariate model, but not in the multivariate model. However, a two-factor-interaction model with PCNA > 5% and mitoses > 6 was highly significant as a predictor of outcome (p < 0.0001). We conclude that PCNA index may be used as an adjunct with mitotic counts in predicting the clinical course of patients with meningiomas.