Proliferation index as a predictor of prognosis in malignant gliomas of childhood.

BACKGROUND

The prognosis for children with high grade gliomas remains somewhat unpredictable because histologic features alone provide an imperfect assessment of the biologic behavior of a given lesion. Whereas some patients experience prolonged disease control after surgery and adjuvant therapy, others with lesions that appear comparable exhibit rapid disease progression and death.

METHODS

Because proliferative activity may provide a potential correlate of biologic aggressiveness, the authors examined the relationship between MIB-1 labeling index and outcome in a series of 29 archival pediatric malignant nonbrainstem gliomas from patients treated consecutively at the study institution between 1975 and 1992, in which clinical, histologic, diagnostic, and therapeutic parameters were previously defined. Three patients who died perioperatively were excluded from outcome analyses. All tumors were rereviewed by two neuropathologists and classified as Grade 3 or 4 lesions based on contemporary guidelines.

RESULTS

Among the specimens from the 26 patients who survived the perioperative period, a striking difference in outcome was apparent between tumors with MIB-1 indices < 12 (n = 10) and those with indices > 12 (n = 16). Median progression free survival was >48 months in the low MIB-1 group compared with only 6 months in the high MIB-1 group (P = 0.014, rank-sum test). Median overall survival was >48 months in the low MIB-1 group compared with only 16 months in the high MIB-1 group (P = 0.012). MIB-1 index remained associated with survival after taking into account the effect of resection extent, which also correlated strongly with outcome in this cohort. Although MIB-1 index was associated with histopathologic grade (Grade 3: 11.9 +/- 9.7 vs. Grade 4: 27.3 +/- 19.0; P = 0.015, Fisher's exact test), it proved to be a much stronger predictor of outcome than histology.

CONCLUSIONS

MIB-1 index may supplement routine histologic classification as a means for improving the accuracy of predicting the biologic behavior of childhood malignant gliomas and may provide a basis for stratifying patients in future malignant glioma studies and refining therapeutic decision-making.