Whole genome SNP scanning of snow sheep (Ovis nivicola).

This is the first report performing the whole genome SNP scanning of snow sheep (Ovis nivicola). Samples of snow sheep (n = 18) collected in six different regions of the Republic of Sakha (Yakutia) from 64° to 71° N. For SNP genotyping, we applied Ovine 50K SNP BeadChip (Illumina, United States), designed for domestic sheep. The total number of genotyped SNPs (call rate 90%) was 47796 (88.1% of total SNPs), wherein 1006 SNPs were polymorphic (2.1%). Principal component analysis (PCA) showed the clear differentiation within the species O. nivicola: studied individuals were distributed among five distinct arrays corresponding to the geographical locations of sampling points. Our results demonstrate that the DNA chip designed for domestic sheep can be successfully used to study the allele pool and the genetic structure of snow sheep populations.

[Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations].

AIM: To study the pattern of complex chromosome damages (CCD) in acute leukemias (AL) and their place in the development of post-transplant recurrences (PTR) of AL. MATERIALS AND METHODS: Cytogenetic and partially molecular biological studies of bone marrow cells were conducted in 10 patients with PTR. Of them, 6 patients were diagnosed as having acute lymphoblastic leukemia (ALL), including T-ALL and Ph-positive ALL in 2 and 4 patients, respectively; and 4 patients had acute non-lymphoblastic leukemia (ANLL), including one case secondarily induced by previous polychemotherapy (PCT) and irradiation. The standard G-band staining technique complemented by multicolor fluorescence in situ hybridization in one of the cases was used. RESULTS: It was shown that CCD had the similar pattern in 4 patients before transplantation and in PTR, progressed in 4 more patients, was absent or unnoticed in the early stage of the disease. The other recurrent chromosomal abnormalities that are worthy of notice are as follows: a) the presence of two Ph chromosomes in the cells of two of the 4 patients with Ph+ ALL; b) the frequent involvement of chromosome pairs 9, 19, 5, and 7 into the numerical and structural rearrangements. CONCLUSION: The important feature of PTR of AL is cellular CCDs, a portion of which is clearly related to previous PCT and may be of pathogenetic value for the development of recurrences.

[Acute lymphoblastic leukemias with translocations (1;19)(q23;p13): a description of 3 new cases and a review of the literature].

AIM: To discuss the specific features of the cytogenetics and clinical manifestations of acute lymphoblastic leukemias (ALL) with balanced and unbalanced translocations (1;19)(q23; p13). MATERIALS AND METHODS: Bone marrow cells with differential staining of chromosomes into G-segments underwent cytogenetic study that was added by fluorescence in situ hybridization in 2 cases. The karyotypes of 3 patients with ALL previously untreated at 5, 18, and 23 years of age were studied. RESULTS: Balanced translocations (1;19)(q23; p13) were found in 2 of the examinees while unbalanced translocation was noted in 1 case. Modal chromosomal classes were 46, 47, and 55-65 if the cells had additional structural (+1q, 6q-, etc.) and numerical chromosomal abnormalities (nonrandom trisomies and tetrasomies of chromosomes of different pairs). CONCLUSION: Translocation (1;19)(q23; p13) is characteristic for patients of different age groups, mainly for those with pre-B cell ALL. It is commonly concurrent with other karyotypic changes, namely, 6q deletion, 1q trisomy, and high hyperdiploidy.

[Phenomenon of hyperexpression of ribosomic cistrons in bone marrow hemopoietic elements in bronchial asthma]. / Fenomen povyshennoi ékspressii ribosomnykh tsistronov v krovetbornykh élementakh kostnogo mozga bol'nykh bronkhial'noi astmoi.

AIM: To study expression of ribosomic cistrons (RC) of bone marrow hemopoietic elements (BMHE) in bronchial asthma (BA). MATERIAL AND METHODS: A total of 37 bronchial asthma (BA) patients were examined. Of them, 20 ones had allergic BA (ABA) and 10--nonallergic BA (NABA). Seven patients received systemic glucocorticoid hormones (SGH). Control included cells of bone marrow from 7 healthy donors. Transcription and maturation of pre-rRNA in BMHE were analysed using bone marrow samples obtained during the sternal puncture (a modified method of Howell and Black). RESULTS: RC activity was high. It depended on BA variant and the disease phase. In ABA high RC activity persisted in remission. GCH suppress RC activity rise. The maximal effect of GCH suppressive action was seen in myeloid lineage, minimal--in erythroid one. The effect is absent in more mature erythroid cells and bone marrow lymphocytes. CONCLUSION: The phenomenon of RC activity rise in myeloid, erythroid and lymphoid lineages of the bone marrow of BA patients may reflect contribution of the bone marrow to formation of BA pathogenesis.

[Elevated expression of argentophilic proteins from the nucleolar organizer regions in myocardium of patients with obstructive hypertrophic cardiomyopathy and mutations in p53 tumor suppressor gene]. / Povyshennaia ékspressiia argentofil'nykh belkov oblastei iadryshkovogo organizatora v miokarde bol'nykh obstruktivnoi gipertroficheskoi kardiomiopatiei i mutatsii v gene opukholevogo supressora p53.

Silver staining for nucleolar proteins was used to evaluate the ribosomal genes activity in cardiomyocytes (Cm) and fibroblast-like cells (FBS) of intraventricular septum, and other regions of the left ventricle. Specimens to be analysed were taken from 7 patients with idiopathic obstructive hypertrophic cardiomyopathy (OHCM). In this group the quantity of nucleoli and AgNORs, reflecting the transcriptional and processing level of pre-ribosomal RNA in all type of cells, was at least 2 and 3 times higher than in patients with essential hypertension and in healthy control, respectively. We suggest that nucleolar hypertrophy in patients with hypertrophic cardiomyopathies, inappropriate to hypertrophy in other pathological conditions, may be most probably of compensatory character, and this may be in part explained by nuclear hyperploidy and chromosomal endoreduplication. We have noted a marked heterogeneity in shape, size and quantity of nucleoli, and in AgNORs of FBC. Nuclei with modulated phenotype containing nucleoli of high activity were revealed. This article presents the first data on p53 mutation identification in patients with advanced OHCM.

Interphase argyrophilic nucleolar organiser regions and nucleolar counts in transitional cell bladder tumours.

AIMS: To see whether a correlation exists between clinicopathological parameters, argyrophilic nucleolar organiser regions (AgNORs), and nucleolar counts in the nuclei of tumour cells in patients with transitional cell bladder carcinoma. METHODS: Paraffin wax embedded sections from a total of 62 cases of primary transitional cell bladder carcinoma were stained with the silver colloid method. The numbers of individual silver grains (AgNORs) in nucleoli and the numbers of nucleoli were counted in 100 nuclei. The correlation between AgNORs and nucleolar counts and patients' sex, tumour grade, disease stage, recurrence pattern, and tumour related survival was analysed. RESULTS: The numbers of nucleoli in tumour cells were higher in male patients (p < 0.032). AgNOR numbers correlated with tumour grade (p = 0.017) and recurrence (p = 0.046). In multivariate analysis, the variation coefficient of AgNOR scores was found to be the only independent predictor of the duration of tumour free period in patients with recurrent disease (p < 0.002). AgNOR scores and nucleolar counts were of no value in distinguishing superficial and invasive tumours or in predicting tumour related survival. CONCLUSIONS: AgNOR scores in transitional cell bladder carcinoma reflect variations in tumour biological behaviour; however, the clinical value of this technique in patients with urinary bladder carcinoma is limited.

AgNORs in the myocardium in ischaemic heart disease complicated by heart failure: a postmortem study.

AIM: To evaluate the interphase ribosomal RNA cistron activity of cardiomyocytes in case with ischaemic heart disease complicated by heart failure. METHODS: Nucleoli were investigated in postmortem myocardium samples from 31 cases with ischaemic heart disease (mean (SEM), 57.4 (6.5) years) with or without severe heart failure (18 and 13, respectively) and from eight healthy people who died in accidents (mean (SEM) 25.3 (4.0) years). Myocardium obtained within one hour after death was frozen in liquid nitrogen. Silver staining for nucleolar organiser regions (AgNOR) was performed with a standard procedure and the mean score obtained. On the basis of these data, the average number of AgNORs per nucleus was determined. The Student's t test was used to compare groups. RESULTS: Compared with controls, the mean numbers of AgNORs per nucleus in cardiomyocytes from ischaemic heart disease patients not complicated with severe heart failure were higher (8.0 v 9.9; p < 0.05), but cases with severe heart failure had a progressive decrease in cardiomyocyte AgNORs. A difference in AgNOR numbers between cases with different ischaemic heart disease courses was found when cases with the same New York Heart Association (NYHA) functional stage III of heart failure were studied. CONCLUSIONS: The significant decrease of AgNORs in cardiomyocytes from cases with severe ischaemic heart disease complicated by heart failure seems to be connected with cardiomyocyte adaptation (a variant of hibernation) to a diminished circulation that, hypothetically, may affect the level of ribosomal RNA synthesis.

Age related decrease of NOR activity in bone marrow metaphase chromosomes from healthy individuals.

AIMS: To present data obtained from human bone marrow preparations from healthy individual showing that the proportion of metaphases with silver stained nucleolar organiser region (AgNOR) chromosomes is associated with the age of the donor. METHODS: Bone marrow preparations from eight Russian and 10 Argentinian healthy individuals donating bone marrow for heterologous transplantation were studied by silver staining. The Russian bone marrow preparations were used directly, while the bone marrow specimens from Argentinian donors were incubated for 24 hours at 37 degrees C in F-10 medium with 15% fetal bovine serum. The slides were silver stained by the one step method of Howell and Black with slight modifications. Thirty metaphases with clearly defined D and G group chromosomes were scored for the numbers of AgNORs. All metaphases that were adjacent to silver stained interphase nuclei were analysed to assess the percentage of AgNOR positive mitoses. The Kruskal Wallis test and Kendall's rank correlation coefficient (rK) were used to assess the relation between age and the percentage of AgNOR positive cells. RESULTS: The mean numbers (SE) of AgNORs per metaphase were 5.06 (0.17) and 5.56 (0.23) for the Russian and Argentinian groups, respectively, with no significant differences between the two groups. The common percentage of AgNOR positive cells decreased significantly as a function of age, with an rK = -0.57 (p < 0.0012). CONCLUSIONS: The percentages of AgNOR negative metaphases in bone marrow from healthy individuals is strongly associated with age and this may be related to age related telomere loss.

AgNORs in cardiomyocytes from surgical patients with coronary heart disease.

AIM: To evaluate the interphase ribosomal RNA cistron activity of cardiomyocytes in surgical patients with chronic ischaemic heart disease by means of the nucleolar organiser region silver staining (AgNOR) technique. METHODS: Nucleoli were investigated in myocardial samples obtained from 46 patients with chronic ischaemic heart disease before, during, and soon after cardioplegia ischaemia. Cryostat sections of 10 microns thickness were air dried, fixed in methanol/glacial acetic acid (3:1) for 15 minutes, rinsed carefully with distilled water, incubated in 2 N formic acid for 10 minutes, and impregnated with silver colloid solution for 2.5-3 minutes at 68-70 degrees C. The lightly counterstained sections were examined under oil immersion at x1000 magnification. For the estimation of AgNOR numbers at least 100 silver stained cardiomyocyte and fibroblast nuclei were counted in each section. On the basis of these data, the mean number of AgNORs in each nucleus was determined. The Student's t test was used to compare the groups tested. RESULTS: The initial mean numbers of AgNORs varied greatly, demonstrating a difference between groups of patients with or without antecedent myocardial infarction (9.5 v 11.0; p < 0.05). During myocardial arrest, the numbers of AgNORs in cardiomyocytes were decreased in all but seven patients, while those in fibroblasts tended to increase. At the stage of reperfusion and myocardial warming, in all but three patients the numbers of AgNORs in cardiomyocytes either normalised or were even higher than the initial value. CONCLUSIONS: The AgNOR count in cardiomyocytes is a very sensitive test for the measurement of cardiac function in surgical patients with chronic ischaemic heart disease and could be useful for monitoring myocardial status during the course of surgery, including cardioplegia. The high risk group for surgery included patients with antecedent myocardial infarction and severe heart failure. It is thought that a reversible nucleolin/fibrillarin/pre-rRNA/small nucleolar RNA modification might account for this fast decline then rise in the AgNOR count in cardiomyocytes at the stages of cardioplegia and reperfusion, respectively.

Nucleoli and AgNORs in Hodgkin's disease.

AIM: To evaluate the morphofunctional characteristics of lymph node cells from patients with Hodgkin's disease by measuring silver stained nucleolar organiser regions (AgNORs). METHODS: Nucleoli in Hodgkin's and Reed-Sternberg (HRS) cells, lymphocytes and prolymphocytes were investigated in cytological smears and histological sections of lymph nodes from 32 patients with Hodgkin's disease, and from 34 patients with reactive lymphadenopathy. According to the Rye histological classification of Hodgkin's disease, three cases were the lymphocyte predominant (LP) type, 14 the nodular sclerosing (NS) type, and 15 the mixed cellularity (MC) type. The investigation was done before treatment, by means of a one step silver staining method. In each case, 50 to 100 HRS cells, lymphocytes, and prolymphocytes were evaluated to determine the mean numbers of nucleoli and AgNORs per nucleus. The nonparametric Wilcoxon Mann-Whitney test was used to compare the groups. RESULTS: The mean numbers of nucleoli and AgNORs were higher in lymphocytes and prolymphocytes compared with those from reactive lymph nodes used as controls. Numbers of nucleoli and AgNORs were higher (not significant) in the NS type of Hodgkin's disease than in the MC type. There was a significant increase in numbers of nucleoli in HRS cells, and their AgNOR counts were increased. The greatest number of nucleoli in HRS cells was found in the NS type. Furthermore, the nucleolar activity of HRS cells was greater in the NS type compared with the MC type (50.2 (SEM 3.9) v 37.7 (2.9) AgNORs per nucleus (p = 0.025)). Comparative analysis of cytological and histological samples showed that the AgNOR score was significantly higher in touch imprints than in tissue sections with tumours of the same histological type. CONCLUSIONS: Assessment of cell activity in Hodgkin's disease patients by silver staining is more convenient and informative in lymph node imprints than in histological sections. The highest expression of interphase ribosomal RNA cistrons found in NS HRS cells is probably explained by their high proliferative activity and elevated production of transforming growth factor 1 which is known to be the most potent cytokine present in the NS subtype of Hodgkin's disease.

Interphase ribosomal RNA cistron silver staining in refractory anaemias with and without excess blasts.

AIM: To evaluate the haemopoietic function of bone marrow blood forming cells in human myelodysplastic syndromes (MDS) by silver staining of nucleolar organiser regions (AgNORs). METHODS: Nucleoli were investigated in bone marrow blast cells and in erythroid, granulocytic, and megakaryocytic cells from 12 haematologically healthy subjects, and from 26 patients with MDS, including 14 with refractory anaemia (RA), nine with RA with excess blasts (RAEB), and three with RAEB in transformation (RAEB-t). The investigation was performed before treatment using a one step silver staining method. In each case 50 to 100 blasts, promyelocytes, myelocytes, immature (pronormoblastic and basophilic normoblastic) and mature (polychromatic normoblastic) erythroid elements, and megakaryocytes were evaluated for the mean numbers of nucleoli and AgNORs per nucleus. Student's t test was used to compare the patient and control groups. Other statistical analyses were carried out by the computer assisted "HEMA" system. RESULTS: Compared with controls, the number of AgNORs in blasts, promyelocytes, immature erythroid elements, and megakaryocytes was decreased, whereas in myelocytes and polychromatic normoblasts it was similar. There was also a difference in the AgNOR scores in blood forming cells from patients with RAEB/ RAEB-t v RA. CONCLUSIONS: The loss of AgNOR sites in cellular series in MDS may result from the decrease of their proliferative potential with disease progression, intrinsic defects in maturation, and extensive apoptosis.

Interphase ribosomal RNA cistron staining in thyroid epithelial cells in Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.

Aim-To evaluate the expression of ribosomal cistrons in human thyroid epithelial cells (TECs) of patients with Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.Methods-TEC nucleoli were investigated in fine needle biopsy specimens from 10 controls, 39 patients with Grave's disease, 15 with Hashimoto's thyroiditis, 56 with benign, and 15 with malignant tumours of the thyroid. A one step silver staining method was applied. In most cases serum concentrations of thyroxine and triiodothyronine as well as goitre size were determined. In every case 100 TECs were evaluated for the mean numbers of nucleoli and for the average number of argyrophilic nucleolar organiser regions (AgNORs) per nucleus.Results-NORs were activated in all patients, but not in controls. The numbers of AgNORs in patients with Grave's disease were closely correlated with thyroxine or triiodothyronine, or both, concentrations and with the size of the thyroid. In patients with Hashimoto's thyroiditis about 30% of TECs nucleoli did not contain AgNORs, whereas others were heavily impregnated with silver. Compared with controls and benign tumours, the nucleoli of carcinomatous TECs were larger and irregular in shape. The mean number of AgNORs per nucleus in malignant cells was higher than that in their benign counterparts.Conclusions-The mechanism by which NORs are activated in TECs varies depending on the type of lesion. The higher AgNOR score in TECs from malignant tumours can be used to distinguish them from their benign counterparts.

[Prognostic significance of the activity of nucleolar organizer regions in megakaryocytes from patients with acute lymphoblastic leukemia]. / Prognosticheskoe znachenie aktivnosti iadryshkovykh organizatorov megakariotsitov u bol'nykh ostrym limfoblastnym leikozom.

Bone marrow films from 20 patients with acute lymphoblastic leukemia (ALL) and 40 patients with acute nonlymphoblastic leukemia (ANLL) were investigated using Ag-NOR staining. The control group comprised 12 donors. The activity of nucleolar organizer regions (NOR) in the whole population of megakaryocytes (MK) and in groups of MK with 1-3, 4-6, 7 and more lobules per nucleus was assessed. The division into groups made it possible to judge about NOR activity in MK with different ploidy. The MK with both high ploidy and high NOR activity in residual megakaryocytopoiesis in patients with ALL are associated with good response to chemotherapy and complete remission, whereas these with low ploidy and low NOR activity suggest poor prognosis. In patients with ANLL no stable correlation between NOR activity and prognosis was found.

Interphase ribosomal RNA cistron staining in chronic myeloid leukaemia.

Aim-To evaluate the haemopoietic function of bone marrow blood forming cells in human chronic myeloid leukaemia (CML) by means of silver staining of nucleolar organiser region (AgNOR).Methods-Nucleoli were investigated in bone marrow blast cells and in erythroid, granulocytic, and megakaryocytic cells from 10 haematologically healthy subjects and from 26 patients with chronic myeloid leukemia (17 in benign phase, nine with blast crisis). The investigation was done before treatment, by means of a one step silver staining method. In every case 50 to 100 blasts, promyelocytes, myelocytes, immature (pronormoblastic and basophilic normoblastic) and mature (polychromatic normoblastic) erythroid elements, and megakaryocytes were evaluated for the mean numbers of nucleoli and for the average number of AgNORs per nucleus. Student's t test was used to compare the patient and control groups. Other statistical analyses were carried out by means of the computer assisted "HEMA" system.Results-Compared with controls, activation of NORs was noticed only in CML blasts, while there was a decrease in NORs in the erythroid elements, promyelocytes, and megakaryocytes. The AgNOR score of polychromatic normoblasts and megakaryocytes started to decrease in the benign stage of CML, whereas a similar decrease in pronormoblasts, basophilic normoblasts, and promyelocytes was detected only in patients with CML blast crisis.Conclusions-The loss of AgNOR sites in cell series in CML may be related to intrinsic defects in their proliferation.

[Functional activity of human thyrocytes in diffuse toxic goiter, autoimmune thyroiditis and thyroid nodules using nucleolar silver staining]. / Funktsional'naia aktivnost' tirotsitov cheloveka pri diffuznom toksicheskom zobe, autoimmunnom tireoldite i uzlovykh obrazovaniiakh shchitovidnoi zhelezy po dannym serebreniia iadryshek.

A comparative study of the thyrocyte nucleolar organizer region (NOR) activity was performed on silver - stained thyroid gland aspiration biopsies from controls, 39 patients with Graves' disease (GD), 15 other patients with Hashimoto thyroiditis (HT), and 71 patients with nodules which underwent surgery. Thyrocyte nucleoli from unchanged thyroid gland were round and small-sized. Their number ranged from 1.34 up to 1.96 per nucleus (mean 1.61 +/- 0.07). The average number of silver (Ag) grains ranged from 3.0 to 6.9 per nucleus (mean - 5.36 +/- 0.36). Compared to the controls the patients with GD revealed thyrocyte nucleoli with increased mean number of AG - grains per nucleus (9.84 +/- 0.24). There was a close correlation between thyrocyte NOR activity, on the one hand, and the level of T3 or T4 hormones and thyroid gland size, on the other. In patients with AT the argentophilla of thyrocyte nucleoli was intermediate between that of controls and patients with GD. This group of patients revealed an increased NOR activity of thyroid gland lymphocytes. Nucleoli of malignant thyroid cells were larger and more irregular than those of benign cells. The mean number of malignant cell nucleoli (2.55 +/- 0.22) was greater than that of the control group (1.61 +/- 0.07; p < 0.05) being identical with those of follicular adenomas (2.47 +/- 0.11) and nodular goiter (2.46 +/- 0.11). The mean number of Ag-grains in the malignant cells (14.9 +/- 0.79) was higher than that in FA (7.95 +/- 0.2; p < 0.0001) and NG (8.0 +/- 0.12; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

[An evaluation of the plastic function of the cardiomyocytes by silver staining of the nucleoli in patients operated on for ischemic heart disease]. / Otsenka plasticheskoi funktsii kardiomiotsitov metodom serebreniia iadryshek u operiruemykh bol'nykh ishemicheskoi bolezn'iu serdtsa.

Examinations of plastic function changes in myocardial cells (MC) from 36 patients with chronic ischemic heart disease were carried out before, during and soon after cardioplegic ischemia. The initial mean number of silver grains in nucleoli varied greatly showing some difference between groups of the patients with (9.5 +/- 0.48) or without (11.0 +/- 0.5) myocardial infarction. During the myocardial arrest this index of MC plastic activity was decreased in all but 7 patients. In contrast to this, it was elevated in most patients tested during subsequent reperfusion. On the basis of these data and parallel histochemical photometric assessment of DNA, RNA and succinate dehydrogenase activity, a hypothesis was suggested which explains the non-standard elevation of ribosomal cistron activity during both myocardial arrest and reperfusion by their compensatory reaction to myocardial injury.

[Determination of nucleolar organizer activity in the differential diagnosis of severe dysplasia and cancer of the large intestine]. / Opredelenie aktivnosti iadryshkovykh organizatorov pri differentsial'noi diagnostike tiazheloi displazii i kartsinomy tolstoi kishki.

The method is based on the selective nucleolar staining with silver salts, the number of silver granules serves as an index of the nucleolar organizer activity which corresponds to the number of RNA-polymerases acting in the cell. The number of silver granules is 5.7, 6.3 and 6.8 per cell in mild, moderate and severe dysplasia, respectively. The histogram of the cell distribution, with regard to the silver grain number, in severe dysplasia is characterized by a shift to the left, and by one high peak. The average number of silver grains is significantly increased in non-invasive and invasive carcinoma and reaches the values of 18.8 and 20.4. A histogram in carcinoma is pulled to the right due to the cells with high content of silver grains and has many low peaks this reflecting variability of cells as to the silver grain content.

[The structure and function of the chromosomal nucleolus organizer regions: the molecular, cytological and clinical aspects]. / Struktura i funktsiia iadryshkoobrazuiushchikh raionov khromosom: molekuliarnye, tsitologicheskie i klinicheskie aspekty.

Numerous data concerning nucleolar organizer region (NOR) structure and function in normal and pathological human cells are analysed. The contents of argentophilic nucleolar proteins vary in the cells tested. The silver-stained test is closely connected with cellular proliferative potentials and differentiation status of the cells. This test also depends on the level of tumor cell malignancy and seemed to be very useful for megakaryocyte and cardiomyocyte studies. In summary, the NOR silver-staining approach is of great value for both fundamental cytological investigations and wide medical practice.

AgNOR staining in benign hyperplasia and carcinoma of the prostate.

We have modified existing techniques for silver staining of nucleolar organizer regions of intact interphase cells by hypotonic swelling and by formic acid treatment to reduce background staining. This allowed the microscopic identification and counting of individual AgNORs in the nucleoli. The method was used on nine adenomatous prostatic samples (including one of normal prostate tissue outside a localized tumor) and on seven prostatic adenocarcinomas. In general, the adenomatous samples displayed fewer AgNORs (mean 13 dots/cell) than did the carcinomas (mean 24 dots/cell). Although no cells with very high AgNOR counts were found in specimens from nonmalignant tumors, two of the adenomatous prostates did have AgNOR profiles that to a large extent overlapped with those of carcinomas. A highly differentiated carcinoma (of which only very small amounts were present in the sample) had low AgNOR counts. The three moderately differentiated carcinomas had more silver-positive material than the nonmalignant prostates but less than the three poorly differentiated carcinomas. The latter tumors also had a substantial proportion of cells with greater than 60 AgNOR counts, something that was never seen in carcinomas with higher differentiation. The data indicate that analysis of silver staining-positive material in intact interphase cells may help distinguish between benign and malignant prostatic tumors and between highly malignant and low malignant carcinomas.