Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III gliomas

The grading of glial tumors has traditionally relied on histological assessment, but the distinction between grade II and grade III gliomas is still a subject of debate. We examined the value of the monoclonal antibody MLB-1 (Ki-67) labeling index (LI) in the differentiation between grade II and grade III gliomas by either the 1993 WHO grading scheme or the St. Anne-Mayo grading scale. The MIB-1 LI in the most densely labeled areas from 80 diffuse cerebral hemispheric gliomas was determined. The tumors included 16 grade II, 31 grade III and 33 grade IV gliomas by the WHO scale. The mean LIs (%) were 0.88 +/- 0.29 for grade II, 8.75 +/- 1.71 for grade III, and 9.12 +/- 1.55 for grade IV gliomas. Analysis of variance indicated a significant difference in mean LIs between grades II and III and grades II and IV (p less than or equal to 0.0001), but not between grades III and N. Seven tumors were classified differently by the 2 systems (grade III by WHO, but grade 2 by St. Anne-Mayo), and all had MIB-1 LI over 3%. Univariate analysis showed that MIB-1 LI with a cut-off point at 1.5% was a significant prognostic factor (p less than or equal to 0.0005). High tumor grade (WHO, p less than or equal to 0.0002; St. Anne-Mayo, p less than or equal to 0.0006) and patient age >50 (p less than or equal to 0.0001) were also significant factors for shorter survival. Using Cox Regression Multivariate Analysis, MIB-1 LI>1.5% was a significant independent predictor of shorter disease survival when paired with tumor grade (p less than or equal to 0.032), patient age (p less than or equal to 0.0065), or gender (p less than or equal to 0.0007). We conclude that the MLB-1 immunoreactivity is useful in distinguishing grade II from grade III gliomas, and maybe more sensitive in assigning aggressive gliomas to grade III than the St. Anne-Mayo grading system.