Comparison of MIB-1 (Ki-67) antigen and bromodeoxyuridine proliferation indices in meningiomas

doi:10.1016/S0046-8177(96)90107-0

Human Pathology

Volume 27, Issue 4, April 1996, Pages 350-354

https://doi.org/10.1016/S0046-8177(96)90107-0 Get rights and content

Abstract

Meningiomas from 40 adult patients were labeled immunohistochemically with monoclonal antibodies to bromodeoxyuridine (BUdR) and the Ki-67 antigen, MIB-1. The meningiomas were classified as classical, or benign (n = 31); atypical (n = 4); or malignant (n = 5). Meningeal sarcomas and hemangiopericytomas were excluded. The patient population consisted of 26 women and 14 men, ranging in age from 26 to 75 years. BUdR proliferation indices ranged from 0% to 5.8%, measurements that were expectedly lower than those for MIB-1, which ranged from 1.5% to 19.3%. MIB-1 proliferation indices were not significantly affected regarding steroid pretreatment or age. These results show a good correlation between the BUdR and MIB-1 proliferation markers (r_s = 0.72; P < .0001), which supports the use of anti-MIB-1 as an alternative labeling tool to BUdR for the determination of the proliferation index in meningiomas, thus avoiding the administration of a potentially mutagenic drug.

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Current decision-making in meningiomas
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Cell death has not been systematically studied in meningiomas but proliferative indices are commonly used. Demonstration of proliferating cell nuclear antigen (PCNA), silver staining for nucleolar organizer regions (AgNOR), immunohistochemistry for MIB-1(Ki-67), and bromodeoxyuridine (BrdU) labeling are the most common methods for demonstrating the proportion of proliferating cell fraction (Langford et al., 1996; Moller and Braendstrup, 1997; Takeuchi et al., 1997; Sandberg et al., 2001; Roser et al., 2004). There is a well-demonstrated correlation between high proliferative indices and recurrences, but this correlation is not exclusive (Langford et al., 1996; Moller and Braendstrup, 1997; Takeuchi et al., 1997; Sandberg et al., 2001; Roser et al., 2004).
The incidence of meningiomas is rising and the number of incidental cases is increasing steadily. The efficiency and the safety of each treatment strategy are also improving over time. Therefore the indications to treat meningiomas are constantly changing. The aim of meningioma treatment is keeping the patient fully functional while achieving long-term relief or prevention from problems related to intracranial tumor growth. This chapter reviews the natural history and treatment results and aims to put together the information for the most objective decision-making in treating meningiomas. Factors acting on the treatment decision such as anatomical localization, symptomatology, variations in tumor biology, recurrence status, age and co-morbidities, operative gains, and patient preference are individually discussed.
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In addition, specific genetic mutations have been found to associate with tumor location among convexity and anterior cranial base tumors (Cuevas et al., 2005; Brastianos et al., 2013). The MIB-1 index of proliferation has been examined in meningiomas (Langford et al., 1996). Not surprisingly, higher overall MIB-1 indices have been found in recurrent tumors, likely due to the more commonly encountered higher grade tumors found on recurrence (Al-Mefty et al., 2004).
We know that the extent of resection is the greatest predictor of long-term survival. However, the potential tradeoff for gross total resection in difficult locations is diminished quality of life. Benign subtotally resected or small incidentally discovered meningiomas may be followed clinically especially in the elderly. In addition, radiosurgery plays a role in the treatment of meningiomas as a primary treatment modality, or as a salvage therapy. Decisions regarding management should be made with an understanding of the natural history and rate of growth. In this chapter we review the known meningioma epidemiology as well as the growth patterns of meningiomas based upon location.
Comparison of the DWI and Gd-EOB-DTPA-enhanced MRI on assessing the hepatic ischemia and reperfusion injury after partial hepatectomy
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To compare two different imaging media, diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) and Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) with perfusion parameters K^trans, K^ep, and relative contrast enhancement index (RCEI), in assessing the liver function via ischemia/perfusion injury (IRI) + partial hepatectomy rat model.
Rats underwent 0, 30 and 60 min of ischemia/reperfusion with 30% of hepatectomy before subjected to Gd-EOB-DTPA-enhanced MRI in addition to ^99mTc-GSA scintigraphy. For ^99mTc-GSA scintigraphy test, the receptor index LHL15, modified receptor index and the blood clearance index HH15 were recorded. Apparent diffusion coefficient (ADC) was evaluated by using both mono- and bi-exponential models, and perfusion parameters K^trans, K^ep, and RCEI were measured. Liver function is tested by measuring activity of serum ALT, AST and PT. Histological analysis was performed by H&E and Ki-67 staining.
^99mTc-GSA dynamic imaging analysis demonstrated that LHL15 was increased and HH15 was decreased as the extension of ischemia/reperfusion time. ADC value estimated by MRI was significantly increased (P < 0.05) in 30 min IRI group compared with 0 min and 60 min IRI groups, respectively. K^trans value was gradually and significantly decreased (P < 0.05) as the extension of IRI time, but there was no significant difference (P > 0.05) in K^ep value between at 30 min and 60 min IRI, and RCEI value was significantly higher (P < 0.05) in 30 min IR compared with 0 min and 60 min IRI group. Serum level of ALT, AST and PT were gradually and significantly (P < 0.05) increased as the extension of IRI time. Histological analysis showed that there was a remarkable difference between 30 min and 60 min IRI, as protein expression of Ki-67 was significantly higher (P < 0.05) in 30 min IRI group.
Fast ADC bi-exponential model in DWI and RCEI in Gd-EOB-DTPA-enhanced MRI showed the good correlation in assessment of liver function after partial hepatectomy, showing consistency with our histological findings. The K^trans in Gd-EOB-DTPA-enhanced MRI could be a potent parameter for assessing the early ischemic injury, but not the severity of the hepatic injury, in accordance with the correlation with our biochemical findings.
Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms
2015, Journal of Steroid Biochemistry and Molecular Biology
Citation Excerpt :
Although not strictly considered part of the “pathway genes”, there are several indicators of net alterations in cell cycle characteristics, including cell proliferation, differentiation, and apoptosis. A marker of a cell in a proliferative phase is the Mib-1 epitope of Ki-67 [37–39]; an informative long-term indicator of proliferation is hTERT, a catalytic subunit of telomerase [40]; and a marker of a cell that can no longer proliferate and is differentiated is p21 [40,41]. Detection of expression of inhibitors (bcl-2) and promoters (bax, bak) of apoptosis can be readily demonstrated in characteristic gradients in crypts of normal colon tissue [40,42–46].
This brief review, based on an invited presentation at the 17th Workshop on Vitamin D, is to summarize a line of the author’s research that has been directed at the intertwined missions of clarifying and/or developing vitamin D and calcium as preventive agents against colorectal cancer in humans, understanding the mechanisms by which these agents may reduce risk for the disease, and developing ‘treatable’ biomarkers of risk for colorectal cancer. The biological plausibility and observational and clinical trial evidence for vitamin D and calcium in reducing risk for colorectal neoplasms, the development of pre-neoplastic biomarkers of risk for colorectal neoplasms, and the clinical trial findings from the author’s research group on the efficacy of vitamin D and calcium in modulating these biomarkers are summarized. Regarding the latter, we tested the efficacy of 800 IU (20 μg) of vitamin D₃ and 2.0 g of calcium daily, alone and combined vs. placebo over 6 months on modulating normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in a randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial (n = 92). The tissue-based biomarkers were measured in biopsies of normal-appearing rectal mucosa using immunohistochemistry with quantitative image analysis, and a panel of circulating inflammation markers was measured using enzyme-linked immunoassays (ELISA). Statistically significant proportional tissue increases in the vitamin D group relative to the placebo group were found in bax (51%), p21 (141%), APC (48%), E-cadherin (78%), MSH2 (179%), the CaSR (39%), and CYP27B1 (159%). In blood, there was a 77% statistically significant decrease in a summary inflammation z-score. The findings for calcium were similar to those for vitamin D. These findings indicate that supplemental vitamin D₃ or calcium can favorably modulate multiple normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in sporadic colorectal adenoma patients.
This article is part of a Special Issue entitled ‘17th Vitamin D Workshop’.
Analysis of factors affecting the long-term functional outcome of patients with skull base meningioma
2011, Journal of Clinical Neuroscience
Citation Excerpt :
This study demonstrated that a high MIB-1 staining index (⩾3%) detected at initial surgery and recurrence in the central skull base, including the petroclival and cerebellopontine angle regions, are both independent predictors for deterioration of the long-term KPS score. Evidence suggests that the growth potential of meningiomas, as assessed by various proliferative indices, can predict patients’ clinical outcomes.11,12,15–19 The nuclear protein Ki-67, present in proliferating cells, has been most investigated as a marker for predicting the biological behavior of meningiomas.
We analyzed the factors that affect the long-term clinical outcome of a series of patients with skull base meningiomas. Clinical records of 73 patients with cranial base meningiomas were reviewed retrospectively, of whom 13 patients experienced a recurrence at various times following the initial surgery. The mean follow-up time was 90.4 ± 21.2 months (range = 60–124 months). Based on the location of the recurrence, patients with recurrence were divided into peripheral (n = 6) and central (n = 7) skull base groups. Of several variables analyzed using a multivariate logistic regression model, “high MIB-1 (Ki-67 proliferation antigen) labeling index” was an independent variable predicting poor long-term functional outcomes. Recurrence of the tumor at the central skull base was also a strong predictor of poor long-term outcomes. An increased proliferative potential, as indicated by a high MIB-1 labeling index, may induce repeated recurrences, eventually leading to worse functional outcomes, particularly for patients with central skull base meningiomas.
The significance of Ki-67/MIB-1 labeling index in human meningiomas: A literature study
2010, Pathology Research and Practice
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.

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Original contributionComparison of MIB-1 (Ki-67) antigen and bromodeoxyuridine proliferation indices in meningiomas

Abstract

Surg Neurol

Hum Pathol

Histological subtypes and prognostic problems in meningiomas

J Neurol

Atypical and malignant meningioma: Any easy diagnostic criteria?

Adv Anat Pathol

Assessment of cell proliferation in histological material

J Clin Pathol

Neuropathology, cell biology, and newer diagnostic methods

Curr Opin Oncol

Prognostic significance of proliferative indices in meningiomas

J Neuropathol Exp Neurol

Bromodeoxyuridine labeling study of intracranial meningiomas: Proliferative potential and recurrence

Acta Neuropathol

Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB-1 and MIB-3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections

J Pathol

New Ki-67-equivalent murine monoclonal antibodies (MIB-1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope

Lab Invest

The cell proliferation-associated antigen of antibody Ki-67: A very large ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins

J Cell Biol

Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas

Histol Histopathol

Original contribution
Comparison of MIB-1 (Ki-67) antigen and bromodeoxyuridine proliferation indices in meningiomas