Nucleolar organizer regions in human maxillary sinus squamous cell carcinoma

A silver colloid technique for nucleolar organizer regions (AgNOR) was applied to paraffin sections of maxillary sinus squamous cell carcinomas (MSSCC) of 25 patients. The patients were divided into two groups, one with MSSCC recurring in the primary lesion after treatment with radiotherapy, chemotherapy and for surgery and one without recurrence. Notable differences between the numbers of NOR in neoplastic epithelia and the normal mucosa were observed ( P = 0.0001), but there were no differences between the numbers of NOR in the recurrent and non-recurrent carcinomas. This investigation found no prognostic importance in the number of AgNOR in MSSCC.     

Nucleolar organizer regions in human adrenocortical disorders

A silver colloid technique to demonstrate nucleolar organizer region-associated proteins (AgNORs) was performed on sections of 39 human adrenal glands, including normal adrenal cortex, bilateral adrenocortical hyperplasia, adenoma, and carcinoma. In mineralocorticoid and glucocorticoid-producing adrenocortical cells, the mean number of AgNORs per nucleus was lowest in the normal adrenal gland and highest in adenoma, with statistically significant differences. The mean number of AgNORs in bilateral adrenocortical hyperplasia was placed between that of normal adrenal and adenoma. AgNOR numbers in morphologically and clinically verified adrenocortical carcinoma (12 cases) were not different from those in adenoma (17 cases). In adrenal cortex, AgNOR numbers may be correlated with increased steroid hormone production but appear to be of little value in discerning malignancy in adrenocortical neoplasms.     

Nucleolar organizer regions and prognosis in renal cell carcinoma

The prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC) was evaluated. NORs were quantified in a series of 182 cases of RCC using the silver-colloid method. The cases were staged according to Robson's method (48 stage I, 26 stage II, 33 stage III, 75 stage IV) and mean NOR numbers for each tumour were correlated with survival over a 5-year period. Localized tumours (stages I and II) with low NOR numbers had an almost 100 per cent 5-year survival. Those patients with clinical evidence of metastases at presentation showed a high mortality, although those with low numbers of NORs had a significantly increased disease-free interval. Statistical analysis using the log rank test indicated NORs to be a significant predictor of survival over the whole series (P = 0.0001) and within each of Robson's stages (P = 0.0008 stage I, P = 0.0154 stage II, P = 0.0009 stage III, P = 0.0001 stage IV). Analysis of data using Cox's proportional hazard model showed mean NOR numbers to be independent of stage as a predictor of survival.     

Nucleolar organizer regions in lymphomas

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 90 non-Hodgkin's lymphomas, five palatine tonsils and five 'reactive' lymph nodes. The method was readily applicable to these preparations and the Ag-NORs were enumerated with ease. A significant difference was found between the numbers of Ag-NORs in the nuclei of low-grade lymphomas (from a mean of 1 to 1.5 per nucleus) and those of high-grade lymphomas (a mean of 4.4 to 6.8 per nucleus). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were not visible. It is suggested that this method, previously largely the province of the cytogeneticist, should find widespread applications in the field of tumour histopathology.     

Nucleolar organizer regions in FNAC smears of breast lesions.

The argyrophil technique for staining proteins associated with nucleolar organizing regions was applied to the fine-needle aspiration cytology smears of 45 cases of breast disease. These included 14 malignant and 31 benign lesions. A correlation with histology sections was done in 12 cases. There was a significant difference between AgNOR count of benign and malignant breast disease with one case out of 45 falling in the "gray" zone of overlap. Infiltrating lobular carcinoma was found to have the lowest NOR counts among the malignant lesions. The smear staining was superior to that on sections, the positive features being lack of background staining and better dispersion of NORs in the nucleoli.     

Nucleolar organizer regions in smooth muscle and breast tumours.

Paraffin sections of formalin fixed tissues, obtained from patients with smooth muscle and breast tumours, were studied by the silver staining technique to quantitate the Nucleolar Organizer Regions (AgNORs) per nucleus and to assess its significance as an independent variable in predicting the behaviour of these neoplasms. Five benign and five malignant tumours of smooth muscle along with ten benign and ten malignant epithelial tumours of breast were studied. Normal myometrium and breast tissue served as controls. Control, benign and malignant tumours of smooth muscle showed mean AgNOR scores of 2.68, 3.89 and 12.50 per nucleus respectively. Control, benign and malignant tumours of breast showed mean AgNOR scores of 1.75, 7.45 and 12.72 per nucleus respectively. These results suggest that quantitative analysis of AgNORs per nucleus is capable of differentiating benign from malignant lesions of smooth muscle and breast.     

Nucleolar organizer regions in gastric carcinoma and its precursor stages

A silver technique for nucleolar organizer regions (AgNOR) was applied to sections from 156 gastric biopsies and gastrectomy specimens. These included normal controls, normal gastric mucosa from carcinoma-bearing stomachs, intestinal metaplasia types I and III, dysplasia and carcinoma. AgNOR counts gradually increased from normal, through intestinal metaplasia, to carcinoma. This finding supports the chronic atrophic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence concept for gastric carcinogenesis. Normal gastric mucosa was different from all lesions, including normal mucosa from carcinoma-bearing stomachs. Significantly higher AgNOR counts were observed in tumours compared to all other lesions except dysplasia. Dysplasia differed from intestinal metaplasia type I but not from type III. Eighty-five per cent of metaplasia cases overlapped with carcinoma and 19% with normal controls. The spread of AgNOR values in intestinal metaplasia reinforces the concept that this lesion is a heterogeneous entity reflecting a dynamic and continuous process. The AgNOR technique may contribute to the assessment of the stage of evolution of 'borderline' lesions.     

Nucleolar organizer regions in cutaneous tumours

A silver colloid technique to identify nucleolar organizer region associated protein (AgNOR) has been applied to 68 cutaneous tumours. Basal cell carcinomas, eccrine tumours, apocrine tumours, and hair follicle tumours had differences in their numbers of AgNORs; these appeared as small black dots in their nuclei. Dermatofibromas and squamous cell carcinomas showed a degree of variability in the number of AgNORs depending on the cellularity of the former and differentiation of the latter. Basal cell carcinomas possessed significantly many more AgNORs per nucleus than the other neoplasms. It is suggested that this technique, previously the province of the cytogeneticist, may be of use in the diagnosis of cutaneous neoplasms.     

Nucleolar organizer regions in uterine sarcomas

Summary Nucleolar organizer regions demonstrable by silver staining technique (AgNORs) are loops of nucleolar DNA transcribing to ribosomal RNA. This report quantifies AgNORs in normal endometrium and myometrium, and in leiomyomas and homologous sarcomas of the uterus. The mean AgNOR number in leiomyosarcomas was significantly higher than that in normal myometrium and that in leiomyomas, whereas no significant difference was observed between normal myometrium and leiomyomas. The mean AgNOR count in low-grade endometrial stromal sarcomas was significantly higher than that in normal endometrial stroma, and significantly lower than that in the high-grade variant of the same tumour. The epithelial component of malignant mixed müllerian tumours exhibited a significantly higher mean AgNOR number than normal endometrial epithelium, and the stromal component of these tumours showed a significantly higher mean AgNOR count than normal endometrial stroma and normal myometrium, respectively. The AgNOR count was significantly correlated with the mitotic rate in leiomyosarcomas, in high-grade endometrial stromal sarcomas, and in the epithelial and mesenchymal portions of mixed müllerian tumours, whereas no statistically significant correlation was observed in low-grade endometrial stromal sarcomas. Increased AgNOR counts have been reported for some kinds of malignant tumours in various organs, compared with normal tissues and benign tumours. This study demonstrates a similar increase when homologous uterine sarcomas are compared with histogenetically related normal and neoplastic tissues. AgNOR counting might be a useful adjunct in the classification and grading of uterine tumours.     

Nucleolar organizer regions of lymphomas in Korea

Nucleolar organizer regions (NORs) are loops of DNA which occur in the nucleoli of cells and which possess ribosomal RNA (rRNA) genes. The numbers and/or configurations of NORs have been thought to be related to cellular activities. To assess the applicability of NORs associated protein (Ag-NORs) in the field of diagnostic histopathology, a silver staining was done in paraffin sections of malignant lymphomas, tonsils and reactive lymph nodes and the numbers of Ag-NORs in the nuclei of low-grade and those of high-grade lymphomas were compared. A significant difference was found between the numbers of Ag-NORs in the nuclei of low-grade lymphoma (a mean of 1.3 per nucleus) and those of high-grade lymphomas (a mean of 4.2 to 8.3 per nucleus). The Ag-NORs were often observed in nuclei in areas where nucleoli themselves were not visible in H&E stain. It is suggested that this method would be of great value in the field of tumor histopathology.     

Nucleolar organizer regions distribution in fine needle aspiration cytological smears from breast lesions

Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.     

Nucleolar organizer regions (NORs) in adenomyosis

Nucleolar organizer regions (NORs) were evaluated in 11 women with adenomyosis. The material, sampled during operations, was silver-stained using the technique of Ploton et al. and verified histopathologically. A hundred cell nuclei per slide were assessed. The examined variables comprised the number of argyrophylic nucleolar organizer regions (AgNORs) in the nucleus, the surface area of a single AgNOR and the position of the AgNORs in the cell nucleus, as well as the AgNORs' coefficient, which were all estimated under a microscope. The parameters were quantitatively assessed using computer image analysis software Multi-Scan Base V.8. Adenomyosis was found to be associated with a significant decrease (up to 60%) in the nuclear area, as well as with a marked reduction (up to 50% as compared with normal endometrium) in the number of AgNOR granules. The total area of AgNORs in the cell nucleus also decreased from 3.55 to 1.57 microm2. There were no significant differences in the number of granules per nucleus either in the control group or in the adenomyosis group. The AgNOR coefficient was found to be lower in adenomyosis compared to normal endometrium.     

Nucleolar organizer regions in melanocytic dysplasia and melanoma

Using silver (Ag) staining to demonstrate nucleolar organizer region-associated proteins (AgNORs), pigmented naevi exhibiting features of melanocytic dysplasia have been examined and compared with benign intradermal and compound naevi and with malignant melanomas. A highly significant difference was found between the numbers of AgNORs demonstrated in benign naevus cells and atypical melanocytes and in malignant melanocytes, suggesting that this technique may have a role in differentiating between difficult melanocytic lesions.     

Nucleolar organizer regions in malignant salivary gland tumors.

Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior.