Mean Number Of Argyrophilic Nucleolar Organizer Regions Research Articles

A Comparison of Proliferative Capacity of Reticular and Erosive Variants of Oral Lichen Planus by Argyrophilic Nucleolar Organizer Regions Method.

Oral lichen planus (OLP), an immune mediated disorder, has been recognized since 1869 and is presented as any one of the six variants. Reticular and erosive are the most frequently encountered. Its proliferative capacity can give some information regarding its progression. We adopted the argyrophilic nucleolar organizer regions (AgNORs) method because of its simplicity to use and dependable results. We evaluated AgNORs in basal, suprabasal, and squamous cell layers. We also compared these three layers within two variants, reticular, and erosive. Thirty clinically diagnosed patients of OLP were included in the study. Reticular and erosive variants were included in our study. This was followed by hematoxylin and eosin staining and later by the AgNOR method. The mean number of AgNORs per nucleus was calculated. Thirteen males and 17 females were the gender distribution. Twenty-three (76.67%) had reticular pattern and seven (23.33%) had erosive pattern. The basal cell layer had the highest mean AgNOR compared to suprabasal and squamous layers. Even among, erosive and reticular variants, the former had higher mean AgNOR counts. Our results suggest that the inflammatory infiltrate close to the epithelial cells can alter the proliferation index for the pattern of protein synthesis of these cells. Moreover, the high proliferative index in OLP can be related to a specific immunologic response. We conclude that AgNOR can be used as a proliferative marker in earlier lesions to detect the severity.

Analysis of Argyrophilic Nucleolar Organizer Regions (AgNORs) in Acute Leukemia in Adults.

The evaluation of argyrophilic nucleolar organizer regions (AgNORs) uses a simple method used in research into neoplasm. Bone marrow aspirates from 70 patients with acute leukemia underwent morphological, immunophenotypic, and genetic assessment and were stained with silver nitrate. In leukemic cells, the mean AgNORs number, mean AgNORs area, and mean AgNOR-area-to-nucleus-area ratio were calculated in patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), and selected risk groups. A higher value of all measured AgNOR parameters was observed in patients with AML compared to the ALL group. In AML patients, a higher mean AgNOR area was found in the ELN3 cytogenetic group compared to the ELN2 cytogenetic group. A higher value of the mean AgNOR count was observed in patients with white blood cells (WBCs) > 12 × 109/L than in the group with WBCs ≤ 12 × 109/L, as well as in patients with >20% blasts in peripheral blood (PB) than in patients with ≤20% blasts in PB. In the ALL group, a higher mean AgNOR-area-to-nucleus-area ratio was found in group with the presence of Philadelphia chromosome Ph(+) than without the Philadelphia chromosome Ph(−). AgNOR parameter analysis is a valuable method for differentiation of AML and ALL in adults.

Argyrophilic nucleolar organizer regions in oral mucosa cells of crack and cocaine users: a cross-sectional study.

The objective of this study was to analyze and compare the presence of argyrophilic nucleolar organizer regions (AgNORs) in exfoliated cells obtained from the buccal mucosa among crack and cocaine users and non-users by the AgNOR staining technique. Seventy-three males ≥ 18years were categorized into two groups: 38 crack and/or cocaine users and 35 non-user volunteers. They were interviewed and responded a questionnaire regarding general health and drug addiction. Exfoliative cytology specimens were collected from the clinically intact buccal mucosa, and cytological preparations were fixed and stained by AgNOR technique. The mean number of AgNORs (p = 0.02) and the percentage of epithelial cells with more than 3 (p = 0.01) and 4 (p = 0.04) AgNORs/nucleus were significantly higher in the non-user group. In conclusion, the frequency and diversity of substances present in the drugs-cocaine, crack, and alcohol-consumed by the volunteers of this study may have influenced the number of AgNORs and the response to damage and consequent effect on protein synthesis.

Argyrophilic nucleolar organizer regions in neoplastic and non-neoplastic hepatocytes bearing Mallory bodies.

The proliferative activity of Mallory bodies (MB)-positive hepatocytes (neoplastic and non-neoplastic) was examined by counting the argyrophilic nucleolar organizer regions (AgNORs). Among 19 cases of hepatocellular carcinoma, the mean number of AgNORs was lower in the MB-positive carcinoma cells than in the negative ones in nine cases, higher in six, and there was no difference in four. In non-neoplastic cases (seven cases of advanced primary biliary cirrhosis and seven cases of alcoholic or nutritional liver injury), the mean number of AgNORs was lower in the MB-positive hepatocytes than that in the negative ones in eight cases, and approximately equal in number in six cases. These findings imply that MB formation does not directly represent the level of proliferative activity of hepatocytes, regardless of whether they are malignant or not.

Expression of Fas and Fas-ligand and analysis of argyrophilic nucleolar organizer regions in squamous cell carcinoma: relationships with tumor stage and grade, and apoptosis

The aim of this study was to investigate whether levels of Fas and Fas-ligand (Fas-L) expression in oral and oropharyngeal squamous cell carcinomas (SCCs) are associated with tumor stage and grade, and to assess whether parameters related to argyrophilic nucleolar organizer regions (AgNORs) correlate with apoptosis in SCC cells and adjacent normal epithelium. Fifty-two specimens taken from the tumoral and neighboring normal tissues of 26 patients with oral and oropharyngeal SCC were analyzed for Fas/Fas-L expression, and 24 specimens from 12 patients for AgNOR parameters. Seventeen (65%) of the tumors were Fas and/or Fas-L-positive (by immunohistochemistry). A significant positive correlation was found between Fas/Fas-L expression and clinical tumor stage ( P < 0.01). Mean AgNOR number per nucleus, AgNOR size and the percentage area of each nucleus occupied by AgNORs (percent of nuclear area) were significantly increased in the SCC cells (4.49 ± 1.28, 4.48 ± 1.42, 5.56 ± 1.22, respectively) when compared with the control neighboring squamous epithelial cells (2.58 ± 0.61, 1.64 ± 0.59 and 4.35 ± 0.62%, respectively) ( P < 0.01). A significant positive correlation was found between the AgNOR parameters and Fas/Fas-L expression as apoptotic markers in the tumoral cells of SCC ( P < 0.05). There was also a significant positive correlation between the AgNOR parameters and the grading of tumors ( P < 0.05). In conclusion, AgNOR count was a strong proliferation marker in patients with SCC, and Fas and Fas-L staining was useful in tumor grading.

Effects of hyperthermia and differentiation on cultured Dunn osteosarcoma cells

We investigated the characteristics of morphology, DNA synthesis and argyrophilic nucleolar organizer regions (AgNORs) on murine Dunn osteosarcoma cells in response to heat (42 °C, 1 h) or dibutyryl cyclic adenosine 3′,5′-monophosphate (Bt 2cAMP). The cell morphology changes to a fibroblast-like appearance with long and thin protoplastic processes with the reduction of DNA synthesis by heat. It is closely similar to a response by Bt 2cAMP. In the presence of 3 mM Bt 2cAMP, the mean number of AgNORs was significantly decreased in 48 h compared with the untreated group. It was increased conversely by heat. Among these responsive cells, we can also find many cells stained without discrimination by the use of AgNORs staining. The present study provides a new clue to support differentiation of osteosarcoma cells from the viewpoint of hyperthermia in vitro.

Expression of topoisomerase IIalpha, Ki-67, proliferating cell nuclear antigen, p53, and argyrophilic nucleolar organizer regions in vulvar squamous lesions.

It was the aim of this study to investigate the expression of topoisomerase IIalpha (topo IIalpha), Ki-67, proliferating cell nuclear antigen (PCNA), p53, and argyrophilic nucleolar organizer region (AgNOR) staining in normal vulvar epithelia (NE, N = 10), vulvar condylomas (VC, N = 24), vulvar intraepithelial neoplasia (VIN, N = 26), as well as squamous cell carcinomas (SCC, N = 22) of the vulva. Formalin-fixed, paraffin-embedded archival tissue sections were immunostained with monoclonal antibodies against topo IIalpha, p53, and PCNA, as well as an affinity-isolated prediluted ready-to-use Ki-67 antibody using a standard immunohistochemical method, and stained with a colloid silver solution for AgNORs. Immunostaining was quantitated by determining the percentage of positively staining nuclei in each sample to express the labeling indices (LIs) by counting the immunoreactive nuclei in 1000 epithelial cells per case for each antibody. In each specimen 200 nuclei were examined using a x100 oil emersion lens, and the mean number of AgNORs per nucleus (AC) was calculated. The LIs for topo IIalpha, Ki-67, and PCNA as well as ACs increased stepwise from NE to VCs, VIN lesions, and SCCs. In contrast to PCNA LIs and ACs, a consistent correlation in all four groups was found for Ki-67 and topo IIalpha, suggesting that the latter is a proliferation-associated marker in these tissues. p53 expression was seen 8.3% of VCs, 30.8% of VIN lesions, and 54.45% of SCCs. p53 LIs were not correlated with LIs for topo IIalpha or Ki-67 in SCCs. The LIs for topo IIalpha, Ki-67, PCNA, p53, and ACs were not related to tumor progression, FIGO stage, or tumor grade in SCCs. This study presents topo IIalpha and Ki-67 as useful proliferation-associated markers of vulvar epithelia.

A histopathological study of lymphoepithelial island formation in labial salivary glands in patients with primary Sjögren's syndrome.

The proliferative status of lymphoepithelial islands in the labial salivary glands of primary Sjögren's syndrome (pSS) patients was investigated by counting the number of argyrophilic nucleolar organizer regions (AgNORs) in epithelial cells constituting the islands. The islands were classified into four groups and evaluated in terms of total area and three discrete zones of the islands. In each pSS group, the mean AgNOR number per total island epithelial cell nucleus was significantly higher than in control ductal epithelial cells. The zonal AgNOR number fluctuated during the process of island formation but became more uniform as the islands developed. Furthermore, statistically significant trends among the four pSS groups were observed in the ratio of T lymphocytes, B lymphocytes and plasma cells surrounding the islands. The results indicated that the islands are highly proliferative once island formation begins and that zonal island cell proliferation may be associated with the inflammatory cells.

Age-related changes in cellular activity in human submandibular glands as evaluated by argyrophilic nucleolar organizer regions.

To examine the age-related changes in cellular activity of epithelial components of human submandibular glands, evaluated on the basis of argyrophilic nucleolar organizer regions (AgNORs). Epithelial components of human submandibular glands were divided into serous acinar cells, mucous acinar cells, intercalated duct cells, striated duct cells, and interlobular duct cells. The mean AgNOR number of each cell type was compared among six age groups. The study was conducted at the Department of Oral Pathology, Tohoku University School of Dentistry, Japan. Necropsy specimens from 66 males and 57 females 1 to 97 years old. In all cell types except for intercalated duct cells, the mean AgNOR number was lowest in the 0-14 year-old group and highest in the 15-29 year-old group. The value then gradually decreased with advancing age and ultimately reached a similar level to that in the 0-14 year-old group. In intercalated duct cells, the mean AgNOR number did not differ significantly between any age group. There were no significant sex-related differences. The cellular activity of almost all components of human submandibular glands rises in adolescence and young adulthood and then decreases with aging. These results suggest that intercalated duct cells are capable of not only proliferation but also division into other components; these cells may thus compensate for the reduced activity of other components in elderly subjects.

Prognostic Value of Argyrophilic Nucleolar Organizer Region (AgNOR) Staining in Feline Intestinal Lymphoma

Limited information is available on prognostic factors for cats with lymphoma. The quantity of argyrophilic nucleolar organizer region (AgNOR) proteins can be used as a measurement of cellular proliferative activity. To determine if AgNORs were of prognostic value for feline intestinal lymphoma, the silver staining technique was performed on paraffin‐embedded sections of 31 cases. Mean number of AgNORs per nucleus ranged from 1.02 to 4.32. Twenty‐four (78%) cats had small AgNORs and 7 (22%) had large AgNORs. All cats were treated identically with a combination chemotherapy protocol. Response to chemotherapy was 87%. Median remission duration and survival times were 120 days and 201 days, respectively. No significant correlation was found between mean number of AgNORs per nucleus or AgNOR size and remission rate, remission duration, or survival time. This study indicates that AgNOR staining is not a useful prognostic factor for cats with intestinal lymphoma.

Prognostic value of argyrophilic nucleolar organizer region (AgNOR) staining in feline intestinal lymphoma.

Limited information is available on prognostic factors for cats with lymphoma. The quantity of argyrophilic nucleolar organizer region (AgNOR) proteins can be used as a measurement of cellular proliferative activity. To determine if AgNORs were of prognostic value for feline intestinal lymphoma, the silver staining technique was performed on paraffin-embedded sections of 31 cases. Mean number of AgNORs per nucleus ranged from 1.02 to 4.32. Twenty-four (78%) cats had small AgNORs and 7 (22%) had large AgNORs. All cats were treated identically with a combination chemotherapy protocol. Response to chemotherapy was 87%. Median remission duration and survival times were 120 days and 201 days, respectively. No significant correlation was found between mean number of AgNORs per nucleus or AgNOR size and remission rate, remission duration, or survival time. This study indicates that AgNOR staining is not a useful prognostic factor for cats with intestinal lymphoma.

Argyrophilic nucleolar-organizer region counts and DNA status in bronchioloalveolar epithelial hyperplasia and adenocarcinoma of the lung

Few studies have investigated more than one cell-biological parameter in bronchioloalveolar epithelial hyperplasia (BEH) and bronchioloalveolar carcinoma (BAC). The authors have examined argyrophilic nucleolar-organizer regions (AgNORs) and DNA status in surgically resected formalin-fixed paraffin-embedded specimens, 27 BEH and 62 well-differentiated adenocarcinomas, including 30 BAC. The authors measured the mean AgNOR count in 200 nuclei from sections of these regions. The authors also quantified DNA distribution in more than 200 cancer cells from sections of these regions, stained with 4′,6-diamidino-2-phenylindole, using a microspectrophotometer. Fourteen lesions were interpreted as atypical BEH. The mean number of AgNORs per nucleus in BEH was 1.25 to 2.63. The mean number of AgNORs was significantly lower in both typical and atypical BEH than in either the bronchial surface epithelial type or the bronchial gland cell type of well-differentiated adenocarcinoma ( P < .05). The mean number of AgNORs in atypical BEH was intermediate between that in typical BEH and that in BAC. Quantitative DNA image analysis showed DNA aneuploidy in 2 of 18 BEHs and 18 of 52 well-differentiated adenocarcinomas. The incidence of DNA aneuploidy increased in this order: typical BEH (0%, none out of 10 lesions) through atypical BEH (25.0%, 2 out of 8 lesions), to adenocarcinoma (34.6%, 18 out of 52 cases). Thus, the incidence of DNA aneuploidy in atypical BEH (25.0%) was intermediate between typical BEH (0%) and BAC (30.0%). These results suggest that atypical BEH may be closely related to BAC.

A Case of Pleomorphic Adenoma with Formation of a Large Cyst: Histomorphometric analysis of tumor cells.

We describe a case of pleomorphic adenoma associated with the formation of a large oval cyst in the right parotid gland in a 54-year-old Japanese man. The proliferative activity of the tumor cells was evaluated by counting the number of argyrophilic nucleolar organizer regions (AgNORs). The tumor, measuring 17×12×12 mm, was a clearly demarcated mass with an almost cystic appearance. It contained whitish cheese-like material. Histologically, the cyst cavity was filled with keratin and was lined by keratinizing squamous tumor cells. Flattened tumor cells were found in the hyalinized stroma. Adjacent islands of squamous metaplastic tumor cells and glandular tumor cells were present. The mean number of AgNORs per nucleus of tumor cells in the glandular portion, mildly keratinizing lining, highly keratinizing basal lining, highly keratinizing superficial lining, and flattened portion was 2.2±0.9, 1.7±1.1, 1.6±1.2, 1.2±0.9, and 1.3±0.8, respectively. Our results suggest that in some pleomorphic adenomas, small squamous metaplastic tumor islands might aggregate and lead to the formation of a large cyst in which the keratinizing tumor cells of the lining have higher proliferative activity than the flattened tumor cells in the hyalinized stroma.

Changes in the Nucleolar Organizer Regions in the Tuberomammillar Region after Dehydration

The existence of efferent connections between tuberomammillary (TM) and the supraoptic (SON) nuclei led us to study the morphological changes at these levels during dehydration induced in rats by repeated administration of hypertonic saline. The dehydration effects are evaluated by three parameters: nucleus area, argyrophilic nucleolar organizer regions (Ag-NOR) area, and mean number of Ag-NORs. These parameters reflect the level of transcriptional activity of the rRNA genes, which in turn is closely related to the protein synthesis activity of the cell. The technique used is argyrophilic staining which labels the nucleolar organizer regions (NORs) of the nucleoli in the neurons and their area, permitting their quantification with an image analysis system. The statistical analysis reflects the sensitivity to dehydration of these structures at TM level. Our results support the regulatory role of vasopressin secretion by SON through the histaminergic pathways arising from TM in rat dehydration processes.

Prognostic significance of nucleolar organizer regions in hepatocellular carcinoma

It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eighty-nine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HCC (mean +/- SD, 3.26 +/- 1.23) was significantly higher than those of normal liver (1.37 +/- 0.13) and cirrhotic liver (1.49 +/- 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (> 3.04) of AgNORs was significantly worse than that of those with a low number (< or = 3.04) of AgNORs. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement.

Prognostic significance of nucleolar organizer regions in hepatocellular carcinoma

It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eighty-nine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HCC (mean ± SD, 3.26 ± 1.23) was significantly higher than those of normal liver (1.37 ± 0.13) and cirrhotic liver (1.49 ± 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (>3.04) of AgNORs was significantly worse than that of those with a low number (≤3.04) of AgNORs. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement.

Clinical significance of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer region (AgNOR) in testicular tumors

Proliferative potential of testicular tumor was assessed by immunohistochemistry using anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody and silver staining of argyrophilic nucleolar organizer region (AgNOR), and the results were compared with clinical course. Fourty-five patients with testicular tumor and 10 normal testicles were investigated. All specimens were fixed with 10% buffered formaliun within 24 hours. The interval between patient's recognition of testicular swelling for the first time and the date for operation was designated as M (months), and the specimen weight was designated as g (gram). Growth rate of the primary tumor was estimated roughly by g/M. PCNA positive rates in seminomas, non-seminomas and normal testes were 70.5 +/- 19.1% (mean +/- S.D.), 80.4 +/- 10.5% and 17.7 +/- 7.8%, respectively. PCNA positive rate in stage I seminoma (64.4 +/- 19.9%) was significantly lower than stage II and III seminoma (83.6 +/- 7.3%) (p < 0.05), but not significant between stage I non-seminoma and stage II, III non-seminoma. The mean numbers of AgNOR per nucleus in seminomas, non-seminomas and normal testes were 8.09 +/- 1.35 (mean +/- S.D.), 6.89 +/- 1.43, 4.18 +/- 1.60, respectively and significantly higher in testicular tumors than normal testes. There were, however, no significant difference between their clinical stages. Logarithmic significant correlation was observed between PCNA positive rate and the growth rate in primary lesion, but no correlation was found between mean number of AgNOR per nuclei and the growth rate. Of the 10 patients with stage I non-seminomas received surveillance policy, four relapsed. Of the 10 patients, 4 of the 6 patients with higher than 75% PCNA positive rate relapsed, whereas, none of the 4 patients with lower than 75% PCNA positive rate relapsed. There were no significant correlation between PCNA positive rate and number of AgNOR. PCNA is more accurate indicator of growth potential in testicular tumor than AgNOR and may predict recurrence in stage I non-seminomatous testicular tumor patients followed by surveillance policy.

Clinical Significance of Argyrophilic Nucleolar Organizer Regions(AgNORs) in Squamous Cell Carcinoma of the Lung

Background: Nucleolar organizer regions(NORs) are chromosomal segments encoding for ribosomal RNA and associated with argyrophilic nonhistone protein. Ribosomal RNA genes ultimately direct ribosome and protein synthesis, and it has been suggested the numbers of NORs detected in the cell may reflect nuclear and cellular activity. This study was performed to evaluate the applicability of AgNORs to the diagnosis of squamous cell carcinoma of the lung. Method: The one step silver methods(AgNORs) was used to stain NORs in the routinely processed, formalin fixed, paraffin embedded sections of 36 cases of squamous cell carcinoma of the lung obtained by surgical resection of primary tumor. In each specimen, 100 tumor cells and 100 normal cells adjacent to the tumor chosen at random were examined under an oil immersion lens at a magnification of . The mean number of AgNORs per nucleus was calculated for each specimen. Results: The mean number of AgNORs per nucleus(mAgNORs) of normal bronchial epithelium and squamous cell carcinoma of the lung was and , respectively. The difference of mAgNOR between normal and tumor tissue was statistically significant(p

The argyrophilic nucleolar organizer regions in ductal carcinoma in situ of the breast. The significance of ploidy and proliferative activity analysis using this silver staining technique.

Two interphase argyrophilic nucleolar organizer region (AgNOR) counts have been correlated with ploidy and proliferative activity in patients with ductal carcinoma in situ (DCIS) of the breast. The first is the mean number of AgNORs (mAgNOR); it reflects ploidy. The second is the percentage of nuclei with greater than or equal to five AgNORs/nucleus (pAgNOR); it correlates with proliferative activity. DCIS of the breast is a heterogeneous group of lesions that is not associated uniformly with invasive ductal carcinoma. A significant number of patients with DCIS will, however, progress to invasive ductal carcinoma. Factors identifying the invasive potential of DCIS in these patients have not been defined clearly. The authors postulated that pAgNOR in DCIS may predict the invasive potential of these lesions. The authors studied 86 cases of DCIS of the breast by the AgNOR silver stain using the two above-mentioned counts. There were 54 comedo and 32 noncomedo DCIS cases. Forty-one cases (47%) were associated with invasive ductal carcinoma. Thirty cases of comedo DCIS (55%) showed mAgNOR counts suggestive of aneuploidy (> or = 2.4/nucleus), whereas only seven cases of noncomedo DCIS (22%) showed such counts (P = 0.001). Cases associated with invasion had higher incidence of aneuploid mAgNOR counts (P = 0.0003). The pAgNOR counts in comedo DCIS ranged from 1% to 36% (median, 11%), whereas in noncomedo DCIS pAgNOR counts ranged from 0% to 22% (median, 7%) (P = 0.007). The 41 cases associated with invasion had pAgNOR counts ranging from 3% to 36% (median, 12%), whereas those not associated with invasion had pAgNOR counts ranging from 0% to 24% (median, 5%) (P = 0.000001). This difference was irrespective of the type of DCIS or mAgNOR counts. Comedo DCIS of the breast may show a higher incidence of aneuploidy and increased proliferative activity and invasive ductal carcinoma than does noncomedo DCIS. Ploidy and proliferative activity, measured by AgNOR staining in DCIS, may have a significant predictive value in identifying the invasive potential of these lesions.

Argyrophilic nucleolar organizer region counts predict survival in thymoma.

The prognosis of thymoma is related mainly to the tumor stage. The prognostic value of argyrophilic nucleolar organizer regions (AgNORs) has been demonstrated in several human neoplasias. Ninety primary thymomas were investigated retrospectively to assess whether AgNOR analysis could offer additional prognostic information. Sections from surgically resected thymomas, routinely fixed in formol and embedded in paraffin, were stained with the argyrophilic method of Ploton. The mean number of AgNORs in the nuclei of 100 tumor cells (AgNOR counts) was calculated for each case. The association between AgNOR counts and survival was assessed by means of uni- and multivariate survival analyses. On univariate analysis, AgNOR counts were associated significantly with 5- and 10-year survival rates (95% and 90%, respectively, for thymomas with 5.58 or fewer AgNORs per cell, but only 55% and 44%, respectively, for tumors with more than 5.58 AgNORs per cell; P < 0.0001). Histologic subtypes of the American classification (P = 0.0006) and clinical stage (P < 0.0001) also were correlated with prognosis. The multivariate survival analysis showed that AgNOR counts (P = 0.001), clinical stage (P < 0.001), and age (P = 0.011) were independent prognostic variables. AgNOR counts were associated with histologic subtypes in the American (P = 0.0001) and European (P = 0.005) classifications and with the clinical stage (P < 0.0001). Moreover, thymoma cells and intermingling lymphocytes showed different numbers of AgNORs and patterns of AgNOR distribution. Analysis of argyrophilic nucleolar organizer regions provides useful prognostic information for patients with thymomas and offers an exact evaluation of the proliferative activity of the neoplastic cells even for thymomas with prominent lymphocytic infiltration.