The role of determining the nucleolar organizers in assessing the evolution of neoplasms


Background: Nucleolar organizer regions are parts of chromosomes that code ribosomal RNA and correlate to cellular proliferation. They have been identified by means of an argyrophilic technique that reveals NORs as black dots in the nuclei. The method has been recently applied in some malignancies, as lymphoma or melanoma. Only few investigations on  hormonal-dependent tumours have been published. Our aim was to investigate on the total number of AgNORs and cell type of endometrial tumors.
Material and Methods: We studied 21 cases of formalin fixed paraffin embedded endometrial tumors including hyperplasia. The number of AgNORs was counted in both epithelial and stromal components. A total of 13 cases were benign and 8 malignant lesions. 
Results: The total number of AgNORs was found to correlate with mitotic counts both in benign lesions and malignancies. The mean number of AgNORs increased from 2.79 in simple endometrial hyperplasia to 10.0 in adenocarcinoma.
Conclusions: Our data indicate that the AgNORs visualization can assist to differentiate between different malignancy grades of endometrial proliferations, especially between complex endometrial hyperplasia and atypical hyperplasia as well as endometrial adenocarcinomas.


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Author Biography

Ana Maria Fatu, "Gr. T. Popa" University of Medicine and Pharmacy Iasi, Romania
Assistent dr.


1. Ploton D, Maneger M, Jeannesson P, Himber G, Pigeon F, Adnet JJ, Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer regions at the optical level, Histochem J 1986;18:5-14.

2. Crocker j, Macartney JC, Smith PJ, Correlation between DNA flow cytometric and nucleolar oraganizer region data in non-Hodgkin’s lymphomas, J Pathol 1988;154:151-6.

3. Pedal WP, et al., Nucleolar organizer regions (AgNORs) in astrocytic tumors, Zentralbl Pathol, 1994, 140(1),89-94.

4. Martin H. et al. .Nucleolar organizer region-associated proteins in cancer cells. Quantitative investigation on gliomas, meningiomas, urinary bladder carcinomas and pleural lesions Anal Quant Cytol Histol 1992 14(4):312-9.

5. Martin H. et al., The significance of the nucleolus organizer region antigen for the differentiation of laryngeal dysplasias and laryngeal carcinoma, HNO, 1996, 44(1):22-6.

6. Giuffrè G, Mormandi F, Barresi V, Bordi C, Tuccari G, Barresi G.- Quantity of AgNORs in gastric endocrine carcinoid tumours as a potential prognostic tool.Eur J Histochem. 2006 Jan-Mar;50(1):45-50.

7. Boquist LL, Nucleolar organizer regions in uterine sarcomas, Virchows Arch A Pathol Anat Histopathol, 1992, 420(4);353-8.

8. Miller B, Flax S, Dockter M, Photopoulos G, Nucleolar organizer regions in adenocarcinoma of the uterine cervix, Cancer, 1994, 74(12):3142-5.

9. Singh M, Prasad S, Kalra N, Singh U, Shukla Y.- Silver-stained nucleolar organizer regions in normal and dysplastic cervical lesions: correlation with DNA ploidy and S-phase fraction by flow cytometry. Oncology. 2006;71(5-6):411-6. Epub 2007 Aug 26.

10. Trere D, Zillbering A, Ditrus D, Kim P, Ginsberg PC, Daskal I, AgNOR quantity in needle biopsy specimens of prostatic adenocarcinomas: correlation with proliferation state, Gleason score, clinical stage, and DNA content, Clin Mol Pathol 1996 49:M209-M213.

11. Winzer JW, Bellach J, Hufnagl P, Long-term analysis to objectify the tumour grading by means of automated microscopic image analysis of the nucleolar organizer regions (AgNORs) in the case of breast carcinoma, Diagnostic Pathology, 2013, 8:56.

12. Giuffrè G, Fulcheri E, Gualco M, Fedele F, Tuccari G.- Standardized AgNOR analysis as a prognostic parameter in endometrial carcinoma, endometrioid type. Anal Quant Cytol Histol. 2001 Feb;23(1):31-9.

13. Heber E, Schwint AE, Sartor B, Nishihama S, Sánchez O, Brosto M, Itoiz ME.- AgNORs as an early marker of sensitivity to radiotherapy in gynecologic cancer. Acta Cytol. 2002 Mar-Apr;46(2):311-6.

14. Trerè D.- Quantitative analysis of silver stained nucleolar organiser regions: a reliable marker of cell proliferation and a promising prognostic parameter in tumour pathology.Clin Mol Pathol. 1995 Aug;48(4):M219-20.

15. G. Emons, M. W. Beckmann, D. Schmidt, P. Mallmann, and for the Uterus commission of the Gynecological Oncology Working Group (AGO) - New WHO Classification of Endometrial Hyperplasias - Geburtshilfe Frauenheilkd. 2015 Feb; 75(2): 135–136. doi: 10.1055/s-0034-1396256 (PMC4361167/)

16. Ploton D, Menager M, Lechki C, Jeannesson P, Visseaux B, Adnet JJ.- Silver staining of nucleolus organizer regions (NORs). Application to the study of nucleolar structure and value in pathology].Ann Pathol. 1988;8(3):248-52.

17. Niwa K, Yokoyama Y, Tanaka T, Mori H, Tamaya T, Silver-stained nucleolar organizer regions in the normal, hyperplastic and neoplastic endometrium, Virchows Arch A Pathol Anat Histopathol, 1991;419(6):493-7.

18. Miller B, Morris M, Silva E, Nucleolar organizer regions: a potential prognostic factor in adenocarcinoma of the endometrium, Gymecol Oncol, 1994, 54(2):137-41.

19. Aubele M, et al, Guidelines of AgNOOR quantitation, Committee on AgNOR Quantitation within the European Society of Pathology, Zentralbl Pathol, 1994, 140(1):107-8.

20. Mahovlic V, Audy-Jurkovic S, Ovanin-Rakic A, Bilusic M, Veldic M, Babic D, Bozikov J, Danilovic Z, Digital image analysis of silver-stained nucleolar organizer regions associated proteins in endometrial cytologic samples, Anal Quant Cytol Histol 1999, 21(1):47-53.

21. Kaushik R, Sharma S, Mahajan V, Gulati A, Sharma BB, AgNORs in endometrial lesions, Indian J Pathol Microbiol, 1999;42(4):451-4.

22. Brustmann H, Riss P, Naude S, Nucleolar organizer regions as markers of endometrial proliferation: a study of normal, hyperplastic and neoplastic tissue, Hum Pathol, 1995, 26(6):664-7.

23. Brustmann H, Riss P, Naude S, Histochemical characterization of endometrial proliferation using AgNOR (nucleolus organizer region), Gynakol Geburtschilfliche Rundsch. 1994;34(4):220-2.
How to Cite
FATU, Ana Maria et al. The role of determining the nucleolar organizers in assessing the evolution of neoplasms. Diagnostic Pathology, [S.l.], v. 2, n. 1, jan. 2016. ISSN 2364-4893. Available at: <>. Date accessed: 04 mar. 2024. doi:


Endometrial Hyperplasia; Endometrial Adenocarcinoma; AgNOR; Mitotic count