The significance of Ki-67/MIB-1 labeling index in human meningiomas: A literature study

Abstract

Histology alone does not always predict the clinical outcome of human meningiomas. Determination of proliferative activity has therefore become an important diagnostic and prognostic tool to identify more aggressive meningiomas, and the Ki-67/MIB-1 monoclonal antibody has become widely used. The aim of this study was to assess the prognostic value of the Ki-67/MIB-1 labeling index (LI) in human meningiomas by a search in the literature. In PubMed/Medline databases, 53 articles were found, and they all showed positive correlations between Ki-67/MIB-1 LI and histological malignancy grade. The average mean labeling indices were 3%, 8%, and 17% for grade I–III meningiomas, respectively. There was, however, considerable overlap of indices between the malignancy groups. Concerning recurrence, meningiomas with a labeling index beyond 4% may indicate an increased relapse rate. Consequently, Ki-67/MIB-1 LI represents a useful predictor of tumor grade and risk of recurrence, however, it must be interpreted cautiously in the individual tumor.

Introduction

Meningiomas account for about one third of primary intracranial neoplasms and represent the largest group of benign tumors. The tumor has its origin in arachnoidal cells. It is most frequently found in middle aged and elderly patients. Most meningiomas are benign and slow-growing and are usually curable after complete removal. However, they have an intrinsic trend to recur, and recurrence depends strongly on tumor grade, proliferative activity, subtype, brain infiltration, and extent of resection [47]. Meningiomas are divided histologically into grade I–III by criteria defined by the World Health Organization (WHO) [30], [47]. However, this grading system is not optimal as long as benign meningiomas may relapse in up to 20% [47]. Limitations of the current grading system to predict tumor behavior have prompted a search for other approaches to identify more aggressive meningiomas, and cell kinetic studies have therefore come into focus based on the hypothesis that recurring tumors comprise a higher number of proliferating cells.

Proliferative activity in tumors can be determined by mitotic counting, flow-cytometric determination of synthesis-phase fraction, and immunohistochemistry using antibodies reactive against various proliferating cellular antigens. Commonly used is the Ki-67/MIB-1 monoclonal antibody, which is reactive against the nuclear antigen Ki-67 expressed during cell cycle (G₁, S, G₂ and M) but absent in G₀ [9]. The percentage of immunoreactive tumor cell nuclei is expressed as a labeling index (LI). In human meningiomas, several studies have shown that an increased Ki-67/MIB-1 LI is positively associated with higher tumor grade and increased risk of recurrence. No standardized procedure for Ki-67/MIB-1 immunostaining exists, and the indices vary largely from one study to another. Despite this, we wanted to search the literature to gain an insight into the role of Ki-67/MIB-1 LI in human meningiomas and to see whether any guidelines can be drawn with regard to histological malignancy grade or risk of recurrence.