Diagnostic Value of Silver-Stained Interphasic Nucleolar Organizer Regions in Breast Tumors

Derenzini, Massimo; Betts, Christine M.; Trerè, D; Mambelli, V; Millis, Rosemary R.; Eusebi, Vincenzo; Cancellieri, Alessandra

doi:10.3109/01913129009076127

Cited by 29 publications

(10 citation statements)

References 17 publications

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“…In this study, we applied the one-step silverstaining technique to the intraductal lesion and main tu mor to see if it would facilitate the distinction between the two lesions. The significant difference (p < 0.01) o f the mean A g -N O R numbers between normal epithelium and main tumor is in agreement with similar studies [16][17][18], It was noteworthy that the difference was also significant (P < 0 .01) between the main tumor and intraductal lesion. Among the subtypes o f intraductal carcinomas, the co medo type is reported to be more aggressive histologically, and cell kinetic studies show such tumors to have a higher proliferation activity [13,19], In our series, however, there was no difference in A g -N O R numbers between comedo carcinoma and the others.…”

Section: Discussionsupporting

confidence: 80%

Nucleolar Organizer Regions in Intraductal Lesions Associated with Invasive Ductal Carcinoma of the Breast

Koyama¹,

Inaji²,

Yamamoto³

et al. 1993

Oncology

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To estimate cell kinetics of intraductal carcinoma present outside the invasive ductal carcinoma of the breast, an argyrophil stain for proteins associated with nucleolar organizer regions (Ag-NOR) was applied on paraffin sections of 28 breast cancers with an extensive intraductal component. The patients chosen for study were comparable to those eligible for breast-conserving surgery in our institute. The mean numbers of Ag-NOR in the nucleus were: normal duct 1.2 ± 0.2 (mean + SD), normal lobule 3.1 ± 1.2, main tumor 10.7 +4.1 and intraductal lesion 7.7 ± 2.6. A significant difference of Ag-NOR numbers was observed not only between the normal epithelium and main tumor (p < 0.01) but also between the main tumor and intraductal lesion (p < 0.01). As for inter-site variation in individual cases, the Ag-NOR number of the intraductal lesion was lower than that of the main tumor in 25 out of 28 cases (89%). These results demonstrate that an intraductal lesion is less aggressive than the main tumor.

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Section: Discussionsupporting

confidence: 80%

Nucleolar Organizer Regions in Intraductal Lesions Associated with Invasive Ductal Carcinoma of the Breast

Koyama¹,

Inaji²,

Yamamoto³

et al. 1993

Oncology

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“…The other parameters, the mean area of AgNOR dots and the MN, had no significant relationship with histological type. Differences of AgNOR expression according to histological grade or type have been reported previously [14,19,37,40].…”

Section: Agnor Status and Survivalmentioning

confidence: 85%

Argyrophilic nucleolar organizer region (AgNOR) area per nucleus as a prognostic factor in breast cancer

Nakayama

Abe

1995

Journal of Surgical Oncology

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Whether argyrophilic nucleolar organizer region (AgNOR) is a predictor of prognosis in breast cancer is controversial. The semiquantitative procedure used to calculate interphasic argyrophilic dots optically is neither reliable nor reproducible. We measured the mean area of AgNOR dots, the mean AgNOR area per nucleus (MA), and the mean AgNOR number per nucleus (MN) by automated image analysis in specimens from 131 patients with breast cancer. Higher MA (> 7.41 microns2), detected in 22 (16.8%) of 131 patients, did not correlate with clinicobiologic variables, except for DNA ploidy status. Overall survival was significantly better in patients with lower MA than in those with higher MA. On multivariate analysis, MA was a significant independent factor, followed by nodal status. These findings indicate that expression of AgNOR should be evaluated in terms of area occupied and that the mean area of AgNOR per nucleus (MA) is an important prognostic factor in the overall survival of breast cancer patients.

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“…Furthermore, from other published datasets [13][14][15][16] we detected amplification of genes of the Pol I transcription machinery in ADH and DCIS, consistent with previous studies reporting the detection of enlarged AgNORs in both premalignant and early breast disease stages. 6,7 Amplification of these genes was detected also in DCIS and matched adjacent IDC tissue, suggesting that upregulation of basal components of the Pol I transcription machinery plays a role in both breast cancer initiation and progression. Here we focused on one of these basal components, RRN3, because studies in different cell contexts show that its overexpression/constitutive activation induces rRNA synthesis and drives cell proliferation, while delaying cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…6 The overall AgNOR area significantly increases with tumor grade and correlates with a poor prognosis. 6,7 Remarkably, enlarged AgNORs have also been detected in benign breast lesions and in situ breast carcinoma, such as ductal carcinoma in situ (DCIS), 6,7 suggesting that increased rRNA synthesis and ribogenesis can be early events of breast tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement of basal components of the RNA Polymerase I transcription machinery

2016

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Upregulation of RNA Polymerase (Pol I)-mediated transcription of rRNA and increased ribogenesis are hallmarks of breast cancer. According to several datasets, including The Cancer Genome Atlas (TCGA), amplification/upregulation of genes encoding for basal components of the Pol I transcriptional machinery is frequent at different breast cancer stages. Here we show that knock down of the RNA polymerase I-specific transcription initiation factor RRN3 (TIF-IA) in breast cancer cells is sufficient to reduce rRNA synthesis and inhibit cell proliferation, and second that stable ectopic expression of RRN3 in human mammary epithelial (HME1) cells, by increasing rRNA transcription, confers increased sensitivity to the anti-proliferative effects of a selective Pol I inhibitor. Further, RRN3-overexpressing HME1 cells, when grown in in vitro 3-dimensional (3D) culture, develop into morphologically aberrant acinar structures lacking a lumen and filled with proliferative cells, thus acquiring a morphology resembling in situ ductal breast cancer lesions (DCIS). Consequently, interference with RRN3 control of Pol I transcription seems capable of both compromising mammary epithelial morphogenetic processes at early breast cancer stages, and driving breast cancer progression by fostering proliferation.

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Diagnostic Value of Silver-Stained Interphasic Nucleolar Organizer Regions in Breast Tumors

Cited by 29 publications

References 17 publications

Nucleolar Organizer Regions in Intraductal Lesions Associated with Invasive Ductal Carcinoma of the Breast

Nucleolar Organizer Regions in Intraductal Lesions Associated with Invasive Ductal Carcinoma of the Breast

Argyrophilic nucleolar organizer region (AgNOR) area per nucleus as a prognostic factor in breast cancer

Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement of basal components of the RNA Polymerase I transcription machinery

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