[Nucleolus organizer regions in pathomorphologic tumor diagnosis]

Morphology and biological behaviour of tumours are closely related to each other and are the main objects of diagnostic tumour pathology. Anaplasia, for example, a well-known cytomorphological criterion of malignancy, is however only an indirect sign of impaired cellular growth control mechanisms. Nowadays, it is a goal of cancer research to investigate these regulatory processes in order to elucidate new diagnostic criteria of malignancy. Silver staining of nucleolar organizer regions (AgNORs) basically meets this new concept. NORs (rDNA) encode for ribosomal RNA and are thus of central importance for the protein synthesis of a cell. Silver stains NOR associated proteins and indicates activated rDNA. Therefore, AgNOR staining covers the proliferative potential of a given cell or a tumour respectively. A prerequisite of reliable application of the AgNOR method to diagnostic tumour pathology is standardization of the technique, which should be based upon scientific results obtained by basic research. Accordingly, in interphasic cells AgNORs are primarily substructures of nucleoli corresponding to the fibrillar centers at the ultrastructural level. This has been shown to be an important criterion to determine the quality of the silver staining reaction. Most artifacts result from inadequate tissue preservation (fixation), unspecific argyrophilic structures and the staining procedure itself. They should either be excluded or--when ever possible--controlled by a proper staining technique, i.e. adjustment to the stainability of every individual specimen. In this respect, digital image analysis proved to be a useful tool. The mean size of AgNORs in small lymphocytes of the same tissue sample is an equivalent of the argyrophilia of a given histological and cytological specimen (internal staining standard). By use of such a standardized staining technique a high diagnostic accuracy is achieved. The proliferative potential of a cell or a tumour can be determined by number, size, staining intensity and distribution of the silver stained dots. In histological tissue sections the quotient of the mean number of AgNORs/cell and the mean area of one AgNOR dot/cell has been shown to be a very sensitive diagnostic parameter. In cytological specimens determination of the total silver stained area per cell is superior to counting of AgNORs simply by eye. Normal and malignant tissue can reliably be discriminated by these morphometric values. In addition, the malignancy potential of the different preneoplastic lesions, e.g. of the urinary bladder, can precisely be described. Flat urothelial lesions with moderate cytological atypia (D2) exhibit AgNOR values in the range of well differentiated papillary carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)