Abstract

The Ki-67 proliferative index is a widely accepted assay for cycling cells within tumor specimens of multiple histological subtypes. While it is not a substitute for the World Health Organization (WHO) grading, the Ki-67 proliferative index is thought to correlate with the biological activity of selected tumors. In the case of intracranial meningiomas, many lesions may be resected multiple times, with radiation therapy juxtaposed between surgical procedures. A retrospective review of 3,900 consecutive patients undergoing intracranial surgical resection at the University of Pittsburgh Medical Center over a five year period was undertaken. Of these patients, 604 had multiple resections. Multiple Ki-67 index scores were available for 42 patients with WHO grade I and II meningiomas, who suffered a recurrence or progression after their initial resection. Evidence of radiation therapy in the interval between pathology reports was also recorded. Data was evaluated for significant differences (p<0.05). WHO grade II meningiomas were more likely to have a higher Ki-67 index score on second resection than WHO grade I tumors (p=0.051). Furthermore, radiation-treated meningiomas demonstrated similar first Ki-67 index scores and higher second Ki-67 index scores (p=0.057 and p=0.022). Male patients tended to have less change in proliferation rates than female patients between the first and second resections (p=0.083), with a greater proportion of female patient tumors demonstrating accelerating proliferation rates. Treatment with radiation was associated with diminishing changes in meningioma proliferation rates compared to non-treated patients for tumors showing both accelerating rates (p=0.067) and decelerating rates (p=0.081). Ki-67 proliferation indices of recurrent or progressive meningiomas indicate that there are potentially distinct types of growth patterns of meningiomas, consisting of accelerating and decelerating proliferation rates. Meningioma growth is related to WHO grade, patient gender, and treatment with radiation. Radiation treatment appears to stabilize or “inactivate” tumor proliferation and thus normalize changes in meningioma growth rates.

Highlights

  • Meningiomas are tumors arising from the coverings of the brain, which are typically benign but may result in significant morbidity depending on the location and size [1-2]

  • The patient demographics and results on Ki-67 values, growth rates, and radiation treatment are provided as Table 1

  • While several seemingly contradictory results have been presented far: (1) meningiomas treated with radiation have significantly higher Ki-67 index scores on a second resection, and (2) it seems that radiationtreated tumors demonstrated slower growth than non-treated tumors

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Summary

Introduction

Meningiomas are tumors arising from the coverings of the brain, which are typically benign but may result in significant morbidity depending on the location and size [1-2] They are classified clinically according to the World Health Organization (WHO) grading scale and classification of brain tumors, which include grades I, II (atypical), and III (anaplastic) for meningiomas [2-4]. The antibody recognizes proliferating cells via a nuclear antigen that is absent in quiescent cells via immunostaining on fresh or frozen tissue. This antigen is expressed during all cell cycle phases, except for G0 and the early portion of G 1. While the function of the Ki-67 protein remains unclear in central nervous system tumors, its presence is used clinically to assess the proliferative index of tumors, for prognostic and diagnostic purposes [6, 18-25]

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