Acta Neurochir (Wien) (1996) 138:1456-1463 Acta Neurochirurgiea 9 Springer-Verlag 1996 Printed in Austria Recurrence of Meningiomas Versus Proliferating Cell Nuclear Antigen (PCNA) Positivity and AgNOR Counting* E. Demirta~ 1, E Yllmaz 1, I. 0vtil 2, and K. 0her 2 Department of Pathology, and 2Department of Neurosurgery, Ege University Medical School, Izmir, Turkey Summary Meningiomas have a wide range of biological potential and clinical behaviour. Histological findings are helpful in recognizing the malignant potential but often fail to correlate with clinical beha- viour. This study attempts to correlate the silver nucleolar organiz- er regions (AgNORs) and proliferating cell nuclear antigen (PCNA) with clinicopathological features of biological activity. Thirty-four completely resected meningiomas were classified as benign [19], atypical [6] and malignant [91. Forty-eight initial and recurrent tumour materials were investigated for staining of AgNORs and immunohistochemistry using monoclonal antibodies against PCNA (clone 19A2 and PC10). There were no differences between the recurrent and non-recurrent cases with regards to AgNOR, PC10 and 19A2 values. Also, no significant difference was found between the primary and recurrent tumours. Both PC 10 and 19A2 labelling indices (LI) showed a significant difference between benign and malignant meningiomas. The 19A2 LI was 0.56 + 0.21 in benign and 2.45 + 16 in atypical meningiomas. The 19 A2 counts showed significant difference between benign and atypical tumours but PC10 values failed to show such a correlation. AgNOR and PCNA indices were not found to be useful in predict- ing recurrences compared to the surgical procedure and histopatho- logical criteria. Keywords: Meningioma; proliferating cell nuclear antigen; nucleolar organizer region. Introduction Meningiomas are classified as benign, atypical and malignant according to histopathological features. Brisk mitotic activity, hypercellularity, high nuclear cytoplasmic ratio, nuclear pleomorphism, nucleolar prominence, uninterrupted sheet-like growth, and presence of zones of necrosis are the features to t * This study was sponsored by the Ege University Research Foundation. describe a meningioma as malignant [6, 17, 37]. Also, brain invasion is an additional important feature for malignant meningioma [6]. Atypical meningiomas may share some but not all of the above-mentioned features with malignant types. However, the relative- ly high recurrence rates of atypical and malignant meningiomas often fail to correlate with histological subtype and clinical behaviour [4, 16]. The signs of aggressive behaviour may be unassociated with histo- logical features of anaplasia. Also, despite "gross total removal", approximately 15% of benign menin- giomas do recur [4]. The poor correlation between histological subtypes and recurrence rate has raised the requirement for techniques detecting the prolifer- ative activity of cells in meningiomas [2, 3, 7, 9, 20, 21, 27, 29, 36, 43]. Crone et al. [9] have shown the correlation between DNA index and proliferation index determined by flow cytometry and recurrence rate of meningiomas. Nucleolar organizer regions (NORs) are loops of ribosomal DNA which are present in the nucleoli of cells and which transcribe to ribosomal RNA [12, 38, 39]. NORs have been demonstrated in tissue sections by a silver colloid technique whereby acidic proteins associated with ribosomal RNA can be visualized as black dots known as silver binding NORs [12, 25, 38, 39]. It has been suggested that the number of AgNORs per cell correlates with cellular activity and may be an indicator of malignancy [8, 12, 14, 21, 29]. The silver colloid techniques for identifying nucleolar organizer regions (AgNOR) have been claimed to predict the biological behaviour of brain tumours including meningiomas but the evaluation of mean