Evaluation of argyrophilic nucleolar organiser regions (AgNORs) in multiple myeloma

Papadhimitriou, Stephanos I.; Daskalopoulou, Dimitra; Tsaftaridis, Panagiotis; Markidou, S.; Stamatelou, Marina

doi:10.1136/jcp.53.6.462

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…Therefore, from a morphological point of view, AgNOR area and count appear to morphologically reflect different aspects behind the neoplastic progression of MM. This might explain the conflicting reports on the questionable prognostic significance of the mean AgNOR count in MM [8,20] .…”

Section: Discussionmentioning

confidence: 62%

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Digital Image Analysis of Mean AgNOR Area Objectively Discriminates between Reactive Plasmacytosis and Multiple Myeloma in Cytologic Smears from Bone Marrow Aspirates

Gunia¹,

Mai²,

Koch³

2008

Pathobiology

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Objective: To differentiate between reactive plasmacytosis (RP) and multiple myeloma (MM) in bone marrow aspirates by assessment of silver-stainable nucleolar organizer regions (AgNORs). Methods: Archival cytologic smears (n = 69) from bone marrow aspirates were retrospectively investigated. Twenty cases had RP and 49 cases MM (24 low-grade, 22 intermediate-grade and 3 high-grade MM). Diagnoses were confirmed by evaluation of the corresponding bone marrow trephine biopsies. Cytologic smears were subjected to AgNOR staining using a standardized silver-staining protocol and assessed by two independent clinical histopathologists using digital image analysis. AgNOR count and area were analyzed in 100 plasma cell nuclei per sample. Results: The mean AgNOR area was found to be significantly (p < 0.001) higher in low-grade MM (mean: 23.4 µm²; range: 19.2–26.7 µm²) than in RP cases (mean: 6.2 µm²; range: 3.8–8.4 µm²). In contrast, mean AgNOR count failed to disclose significant differences between low-grade MM (mean: 5.36; range: 1–7) and RP (mean: 3.68; range: 1–6). Conclusion: Digital image analysis of the mean AgNOR area might be used as a diagnostically useful adjunct to aid objectively in the challenging differentiation between RP and MM in bone marrow aspirates.

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Section: Discussionmentioning

confidence: 62%

“…The mean AgNOR count has been suggested to be an index for M protein synthesis rather than an independent prognostic factor in MM [20] . Therefore, from a morphological point of view, AgNOR area and count appear to morphologically reflect different aspects behind the neoplastic progression of MM.…”

Section: Discussionmentioning

confidence: 99%

Digital Image Analysis of Mean AgNOR Area Objectively Discriminates between Reactive Plasmacytosis and Multiple Myeloma in Cytologic Smears from Bone Marrow Aspirates

Gunia¹,

Mai²,

Koch³

2008

Pathobiology

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“…29 We observed increased nucleolar number and area in human MM tumor samples that are t(4;14) positive and in ACA11 overexpressing cell lines. 32 In addition, higher NOR counts in MM patients are directly associated with poorer survival. 30 Once activated, NORs are associated with a set of proteins involved in ribosome biogenesis, which activate RNA Polymerase I transcription of rDNA genes.…”

Section: Discussionmentioning

confidence: 99%

“…31 The clinical relevance of NORs in MM patients has been demonstrated by correlating increased NOR number in stage III MM compared to stage I. 32 In addition, higher NOR counts in MM patients are directly associated with poorer survival. 33 Together these data provide evidence that ACA11 overexpression drives a key nucleolar phenotype in MM associated with t(4;14) chromosomal translocation and poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

The snoRNA target of t(4;14) in multiple myeloma regulates ribosome biogenesis

et al. 2019

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The orphan small nucleolar RNA (snoRNA) ACA11 is overexpressed as a result of the t(4;14) chromosomal translocation in multiple myeloma (MM), increases reactive oxygen species, and drives cell proliferation. Like other snoRNAs, ACA11 is predominantly localized to a sub‐nuclear organelle, the nucleolus. We hypothesized that increased ACA11 expression would increase ribosome biogenesis and protein synthesis. We found that ACA11 overexpression in MM cells increased nucleolar area and number as well as argyrophilic nuclear organizing regions (AgNORs). Supporting these data, samples from t(4;14)‐positive patients had higher AgNORs scores than t(4;14)‐negative samples. ACA11 also upregulated ribosome production, pre‐47S rRNA synthesis, and protein synthesis in a ROS‐dependent manner. Lastly, ACA11 overexpression enhanced the response to proteasome inhibitor in MM cells, while no effect was found in response to high doses of melphalan. Together, these data demonstrate that ACA11 stimulates ribosome biogenesis and influences responses to chemotherapy. ACA11 may be a useful target to individualize the treatment for t(4;14)‐positive myeloma patients.

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“…[8,9] Certain reports suggest that AgNOR numbers in interphase are a refl ection of their proliferation rate rather than degree of malignancy. A rapidly dividing tumor population is more likely to have a greater proportion of cells in the early stages of G 1 phase before individual NORs have associated together and are therefore more likely to be observed in greater numbers.…”

Section: Discussionmentioning

confidence: 99%

Morphometric evaluation of AgNORs can help in identifying incipient cellular alterations in clinically normal-appearing oral mucosa adjacent to oral squamous cell carcinoma

Thippeswamy¹,

Einstein²,

Mujib³

et al. 2014

J Dent Res Sci Develop

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Background: The value of silver staining of nucleolar organizer region (AgNOR) counts as a diagnostic aid and has been reported in several neoplastic entities. Previous studies have proven the value of the morphometric evaluation of AgNOR in the detection of incipient cellular alterations. Materials and Methods:Computer-assisted morphometric analysis of AgNORs was performed in normal oral mucosa and mucosa adjacent to oral squamous cell carcinoma (OSCC). Morphometric values were compared between the study groups. Descriptive data were presented as mean ± SD; Student t-test was used for assessing the possible signifi cant difference between the study groups. Results:The results of the present study showed a signifi cant difference in all the four AgNOR-related parameters from epithelium adjacent to OSCC compared to the normal oral mucosa. Conclusion:The nucleolar organizing region (NOR)-related parameters assessed are biologically informative and easy to monitor routinely at a pathology laboratory. Further, AgNORs provide valuable data by which we can study the spectrum of nuclear changes in malignant and premalignant lesions.level and these should be regarded as the true interphase counterpart of the NORs present on the fi ve human acrocentric chromosomes, namely chromosome number 13, 14, 15, 21, and 22. The expression "AgNOR" designates, conveniently, the silver-stained NOR proteins. The argyrophilic silver staining of nucleolar organizer region (AgNOR) technique is remarkably specifi c as a means for the detection of NORs that demonstrates by virtue of silver binding to a wide array of NOR-associated Proteins (NORAPs). These include ribonucleic acid (RNA) polymerase I, C 23 protein (Nucleolin), and B 23 protein. [4] The patterns of NOR by size and distribution, as visualized by silver staining (AgNORs), are known to vary with different cell cycle stages. The number of individual dots may increase during the mitotic phase, whereas in the G 1 phase, there is a tendency for the dots to decrease in number, with a concomitant increase in AgNOR area. Computerized image analysis of the number of AgNORs, AgNOR area, size, and shape is an accurate and reproducible method to study the proliferative potential and cell stability of the tissue analyzed. IntroductionOral mucosa adjacent to squamous cell carcinoma (OSCC) is an interesting model for studying the biology of epithelia, which may have higher risk for malignant change in keeping with the premalignant hypothesis.[1] OSCC usually develops at a single site of the mucous membrane and expands in depth and laterally. Slaughter et al., [2] have suggested that carcinoma would arise from multifocal areas of precancerous change. Thus, lateral growth of the tumor may be due in part to progressive change to cancer of peripheral cells and not solely to expansion and destruction from preexisting malignant cells. Moreover, mucosa may be infl uenced by the paracrine effects of various growth factors produced by the cancer. [1] Nucleolar organizing regions (NORs) are loo...

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Evaluation of argyrophilic nucleolar organiser regions (AgNORs) in multiple myeloma

Cited by 7 publications

References 25 publications

Digital Image Analysis of Mean AgNOR Area Objectively Discriminates between Reactive Plasmacytosis and Multiple Myeloma in Cytologic Smears from Bone Marrow Aspirates

Digital Image Analysis of Mean AgNOR Area Objectively Discriminates between Reactive Plasmacytosis and Multiple Myeloma in Cytologic Smears from Bone Marrow Aspirates

The snoRNA target of t(4;14) in multiple myeloma regulates ribosome biogenesis

Morphometric evaluation of AgNORs can help in identifying incipient cellular alterations in clinically normal-appearing oral mucosa adjacent to oral squamous cell carcinoma

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