Cell proliferation in intracranial tumours: selective silver staining of nucleolar organizer regions (AgNORs). Application to surgical and experimental neuro‐oncology

Abstract

A novel tool in diagnostic and experimental pathology, the AgNOR-technique, which consists of visualization of ribosomal gene activity by selective silver staining, was applied to 144 cytological specimens of human tumours of the nervous system. The number of silver-stained nucleolar organizer regions (AgNORs) was correlated with the biological behaviour of the tumours investigated; low AgNOR number were observed in benign neoplasms such as meningiomas and schwannomas and higher AgNOR numbers in glioblastomas and metastases. The mean AgNOR number per cell was 3.15 in astrocytomas, 4.5 in anaplastic astrocytomas and 5.86 in glioblastoma multiforme. Benign and malignant lesions showed different distribution patterns of AgNORs, with few but centrally located AgNORs in benign, and multiple but scattered AgNORs in malignant tumours. AgNOR number per cell and AgNOR area revealed an inverse relationship (correlation coefficient -0.15, linear regression). In addition to the human tumours, two N-nitroso-N-ethyl-urea (NEU) induced tumors in BD-IX rats a mixed glioma (G-XIII) and a malignant schwannoma (N-XII), were investigated. Twelve G-XIII gliomas revealed homogenous AgNOR-counts (standard error of the mean less than 10%), with absolute values between the values obtained for human glioblastomas and metastases. Seven N-XIII subcutaneously transplanted schwannomas revealed higher AgNOR values than human schwannomas, but lower than experimental gliomas. It is concluded that the AgNOR method, as a technique for visualization of ribosomal gene activity, is valuable for assessing proliferative activity and malignancy in both diagnostic and experimental neuropathology.

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“…Nucleolar organizer regions (NORs) are the loops of repetitive DNA sequences, which transcribe to ribosomal RNA (rRNA). [ 33 ] The numbers of silver stained‐nuclear organizer regions (AgNORs) positive cells are directly proportional to the speed of cell proliferation. Furthermore, the high numbers of AgNORs positive cells are indicative of tumor malignancy.…”