Indian Journal of Dental ResearchIndian Journal of Dental ResearchIndian Journal of Dental Research
HOME | ABOUT US | EDITORIAL BOARD | AHEAD OF PRINT | CURRENT ISSUE | ARCHIVES | INSTRUCTIONS | SUBSCRIBE | ADVERTISE | CONTACT
Indian Journal of Dental Research   Login   |  Users online: 26

Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size         

 


 
ORIGINAL RESEARCH Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 2  |  Page : 141-146
Argyrophilic nucleolar organizer regions in inflammatory, premalignant, and malignant oral lesions: A quantitative and qualitative assessment


Department of Oral and Maxillofacial Pathology, Sri. Ramachandra Dental College and Hospital, Sri. Ramachandra University, Porur, Chennai - 600 116, Tamil Nadu, India

Click here for correspondence address and email

Date of Submission28-May-2007
Date of Decision20-Nov-2007
Date of Acceptance23-Nov-2007
 

   Abstract 

Background and Objective: Argyrophilic nucleolar organizer regions (AgNORs) have found widespread application in the past, especially in tumor histopathology. This study was undertaken to evaluate the significance of various AgNOR parameters and to assess their role in differentiating hyperplastic, premalignant, and malignant lesions.
Materials and Methods: The study sample consisted of archival biopsy specimens of ten squamous cell carcinomas, ten premalignant lesions, and five inflammatory lesions. Two biopsies from normal mucosa acted as control. AgNORs were assessed both quantitatively and qualitatively. The data were analyzed using Student's independent t-test, one-way analysis of variance (ANOVA), and multiple range test (Tukey-HSD).
Results: Quantitatively significant difference existed in the number of AgNORs between the normal mucosa, inflammatory lesions, and carcinomas, but the premalignant lesions failed to differ significantly from the normal mucosa. The number of AgNORs was found to be related to epithelial proliferation. Qualitatively, in terms of size, shape, and pattern of distribution, the normal mucosa and inflammatory lesion were alike, but the premalignant and malignant lesions differed significantly from the normal, with a marked degree of AgNOR pleomorphism being observed in carcinomas.
Conclusions: AgNOR quantity is strictly proportional to the proliferative activity of the cell and does not necessarily indicate malignancy. It is the qualitative characteristics of AgNOR that help to differentiate hyperplastic, premalignant, and malignant lesions.

Keywords: AgNORS, nucleolar organizer regions, oral lesions, oral cancer, premalignant lesions/conditions, qualitative and quantitative assessment

How to cite this article:
Elangovan T, Mani N J, Malathi N. Argyrophilic nucleolar organizer regions in inflammatory, premalignant, and malignant oral lesions: A quantitative and qualitative assessment. Indian J Dent Res 2008;19:141-6

How to cite this URL:
Elangovan T, Mani N J, Malathi N. Argyrophilic nucleolar organizer regions in inflammatory, premalignant, and malignant oral lesions: A quantitative and qualitative assessment. Indian J Dent Res [serial online] 2008 [cited 2020 Feb 17];19:141-6. Available from: http://www.ijdr.in/text.asp?2008/19/2/141/40469
Nucleolar organizer regions (NORs) are loops of DNA that transcribe for ribosomal RNA (rRNA). They are located on the short arm of chromosomes 13, 14, 15, 21, and 22. [1],[2] Associated with these regions are certain acidic and argyrophilic, non-histonic proteins called NOR-associated proteins (NORAPs). NORs can be demonstrated in tissue sections by staining their associated proteins with colloidal silver and these silver-stained reaction products represent the argyrophilic nucleolar organizer regions (AgNORs). The specificity and simplicity of the AgNOR staining procedure has led to widespread application of this technique in human pathology. NORs reflect protein synthesis and are known to increase in number during malignancies. Several studies [3],[4],[5],[6] have shown that AgNOR counts can be used to differentiate between benign and malignant lesions, whereas a few others [7],[8] have stated that it is the morphological characteristics of AgNOR that is more informative than their absolute numbers. However, contradicting reports [9],[10],[11] are also available that deny the potential usefulness of AgNORs, and so ambiguity still exists over the exact role of the different AgNOR parameters.

The mucous membrane lining the oral cavity is capable of manifesting a wide spectrum of changes due to various known and unknown factors. These changes vary from inflammatory lesions and benign keratosis to premalignant and malignant lesions. In view of the prevailing uncertainty over the use of AgNORs in clearly differentiating between hyperplastic, premalignant, and malignant lesions, this study was undertaken to assess (a) AgNORs on a wide spectrum of normal, inflammatory, premalignant, and malignant lesions of the oral mucosa both quantitatively and qualitatively, (b) the potential usefulness of AgNORs in assessing the malignant and premalignant status of oral lesions, and (c) the role of AgNORs in differentiating inflammatory from malignant epithelial proliferation.


   Materials and Methods Top


Material for the study consisted of 25 archival biopsy specimens which included 10 squamous cell carcinomas (5 well differentiated and 5 moderately differentiated), 10 premalignant lesions (5 oral submucous fibrosis and 5 leukoplakias), and 5 inflammatory lesions (pyogenic granuloma), all accessioned by the Department of Oral and Maxillofacial Pathology, Sri. Ramachandra Dental College and Hospital, Chennai, during a 2-year period (2002-2003). Two biopsies from normal buccal mucosa were included as control specimens. The entire study sample was divided into the following groups: group I - control; group II - pyogenic granuloma; group III - oral submucous fibrosis; group IV - leukoplakia; group V - well-differentiated squamous cell carcinoma (SCC); and group VI - moderately differentiated SCC.

AgNOR staining procedure

The AgNOR technique was adapted from that described by Crocker and Nar. [12] Four-microns-thick sections were made for each case, deparaffinized in xylene, and hydrated through decreasing grades of ethanol to double-distilled deionized water. The sections were then reacted with freshly prepared silver colloidal solution (containing one part by volume of 2% gelatin in 1% formic acid and two parts by volume of 50% aqueous silver nitrate solution) in a closed Coplin jar for 35 min at room temperature, ensuring a dark environment throughout the reaction time. The silver colloidal solution was washed with double-distilled deionized water. The sections were then treated with 5% sodium thiosulphate for 5 min and washed in double-distilled deionized water, dehydrated through increasing grades of ethanol, cleared in xylene, and mounted.

AgNOR count - quantitative assessment

For each case, 100 keratinocytes in the full width of the epithelium were examined using the ×100 oil immersion objective of the light microscope. By careful focusing, AgNOR dots were counted; both intranucleolar and extranucleolar dots were included in the counting regime. However nuclei that were overlapped or those with indiscernible AgNORs were excluded. Mean AgNOR values were calculated for each case and group means were derived. Statistical analysis of the data obtained was performed using Student's independent t-test, one-way analysis of variance (ANOVA), and Tukey test for honestly significant difference (Tukey-HSD).

Morphological characteristics - qualitative assessment

Morphological variations of AgNORs were assessed in terms of size and shape of the individual AgNOR dots and their pattern of distribution, as defined by Warnakulasuriya and Johnson, [13] who identified three different patterns of AgNOR distribution, viz, type I - single or few large dots within the nucleus, representing the nucleolus; type II - discrete small dots within the nucleolus; and type III - fine black dots dispersed throughout the nucleoplasm.


   Results Top


AgNORs were strictly located within the nucleus and were distinctly stained in black, being visible as dots or blobs that were either round or oblong. The rest of the nucleus stained yellow-brown. By careful control of the silver staining procedure it was possible to reduce the background staining to a minimum level, so that it did not interfere with the identification and/or counting of AgNORs.

Quantitative

The mean AgNOR count of each group and the statistical test results are shown in [Table - 1]. The mean AgNOR count ranged from 1.77 (normal mucosa) to 8.47 (moderately differentiated SCC). The values for the premalignant lesions were lower than that of inflammatory lesion and carcinomas. One-way ANOVA indicated a significant difference among the different groups ( P < 0.0001). The Tukey-HSD test showed that groups VI and V differed significantly from other groups ( P < 0.05). On further analysis [Table - 2], we noticed that submucous fibrosis (group III) and leukoplakia (group IV) did not show any significant difference from the normal. Pyogenic granuloma (group II), well-differentiated SCC (group V), and moderately differentiated SCC (group VI) showed statistically significant higher AgNOR counts than the control group. The maximum significance was seen in case of moderately differentiated SCC, with a P -value < 0.0001. Thus, the results reveal that inflammatory and malignant lesions differ significantly from normal mucosa, but the premalignant lesions fail to do so. Similarly, it can be inferred that inflammatory lesions differ significantly from both premalignant and malignant lesions. A significant difference is also noticed between premalignant and malignant lesions. Analysis of the mean AgNOR counts between the individual lesions in the premalignant and malignant categories reveal that no significant difference exists between the two premalignant lesions of submucous fibrosis and leukoplakia (P = 0.20); However, a significant difference (P = 0.007) does exist between the individual malignant lesions, viz, well-differentiated and moderately differentiated SCC.

Qualitative

The morphological assessment of AgNORs based on their size, shape, and the pattern of distribution revealed certain differences and characteristics among the various study groups. In case of control (group I), the individual AgNOR dots were medium sized, uniformly round or oval [Figure - 1], and belonged to the type I pattern of distribution. In pyogenic granuloma (group II), the individual dots grossly resembled those in group I [Figure - 2], but were smaller in size and also exhibited a type I pattern of distribution. In case of submucous fibrosis (group III) and leukoplakia (group IV), the AgNORs were not so uniformly round or oval. Some of them were slightly larger in size, irregular in shape [Figure - 3],[Figure - 4], and exhibited mixed type I and type II patterns of distribution. This variation in size and shape appeared to be due to overlapping/clumping of the otherwise discrete and smaller AgNOR dots seen in type II. In case of SCC, the AgNORs were distributed throughout the nucleus and predominantly belonged to the type III pattern of distribution [Figure - 5]. Sometimes these AgNORs also appeared very fine, minute and numerous, and distributed throughout the nucleoplasm, giving rise to a granular appearance. Additionally the individual dots also showed abnormal appearances like the signet ring, spidery web, [Figure - 6] and oblong and linear patterns. Such abnormal appearances of AgNORs were seen to a greater degree in case of moderately differentiated SCC compared to well-differentiated SCC.


   Discussion Top


NORs are the sites of ribosomal RNA synthesis that reflects protein synthesis. AgNORs that stain for NOR-associated proteins is known to increase with increase in cell ploidy, increased transcriptional activity, and in states of active cell proliferation. [2],[12] AgNORs have found widespread application in tumor histopathology in assessing the growth potential [14],[15],[16] and malignant potential [17] of tumors, in distinguishing between benign and malignant neoplasms, [3],[4],[5],[6] to assess the prognosis [18],[19],[20],[21] and also to evaluate the risk of recurrence. [22] Few studies have been carried out so far comparing AgNOR staining in normal, reactive, and malignant tissues. One such study was done in pleural mesothelial tissue [23] and another in endometrial tissue, [24] both showing significant differences among the different groups.

In the field of oral pathology, AgNORs have been used by various investigators to differentiate between odontogenic cysts and tumors, [25] to distinguish recurrent and nonrecurrent giant cell lesions of the jaws, [26] in predicting the biological behavior of oral submucous fibrosis, [27] in differentiating oral squamous cell carcinoma from benign and reactive lesions, [13] and also in detecting incipient cellular alterations. [28],[29] AgNORs have been shown to be useful as a marker of tumor progression, [30] to predict the response of tumor to treatment, and to detect residual viable tumor. [30],[31] Most of the studies on AgNOR have been done focusing on its application in neoplastic and related conditions only. A thorough search of the dental literature does not show the application of this technique for studying oral inflammatory lesions representing non-neoplastic epithelial proliferation and its comparison with the normal. With this in mind, this study aimed to assess AgNORs in normal tissue and in inflammatory lesions, in addition to the premalignant and malignant oral lesions. Special attention was given to assess AgNORs both quantitatively and qualitatively.

The results of the present study clearly indicate significant differences in the mean AgNOR count among the different study groups and also a steady increase in the count from the normal mucosa to inflammatory lesions and to squamous cell carcinoma. An earlier study [32] showed variable AgNOR counts between potentially malignant lesions and SCC of the lower lip. In the current study, the premalignant group, comprising oral submucous fibrosis and leukoplakia, exhibited significantly lower AgNOR counts compared to SCC, but this did not vary much from that of the normal mucosa. Oral submucous fibrosis and leukoplakia are the two most common lesions representing the group of conditions/lesions categorized as premalignant. The selection of these two lesions was done on a clinicopathological basis as per the WHO definition. Histologically these lesions showed mild epithelial abnormalities (? atypia), without any apparent proliferative activity. Hence they exhibited a lower AgNOR count, almost similar to that of the normal mucosa. Moreover, oral submucous fibrosis characterized by epithelial atrophy, demonstrated the lowest mean AgNOR count among the study groups. On the other hand, pyogenic granuloma characterized by epithelial hyperplasia showed a definite increase in the AgNOR count, intermediate between that in the normal mucosa and SCC. The results thus suggest that AgNOR quantity is strictly proportional to the proliferative activity of the epithelium, thus confirming the earlier studies. [33],[34] The findings also suggest that the quantitative study of AgNOR is not a reliable tool to assess the premalignant status of any lesion in the absence of epithelial proliferation which may be neoplastic or otherwise.

AgNOR numbers have also helped to differentiate various grades of malignancies. Correlations of AgNOR numbers with histological grades of tumors of central nervous system [14] and lung carcinoma [35] have been documented. One such study on oral SCC [36] revealed significant differences in mean AgNOR counts between poorly, moderately, and well-differentiated lesions and also showed that the mean count increased gradually from well-differentiated to moderately differentiated and to poorly differentiated SCC. Similar results were observed in this study, wherein moderately differentiated SCC showed a higher AgNOR count than well-differentiated SCC. Moderately differentiated SCC is more aggressive and highly proliferative compared to well-differentiated SCC and hence the difference in the mean counts is on expected lines, thus confirming the available reports.

Qualitative assessment of AgNORs based on their size, shape, and pattern of distribution showed significant difference among the different study groups and these findings seem to give more information about the malignant status of the lesions. The appearance of the individual AgNOR dots was almost similar in groups I and II (control and pyogenic granuloma). They were regular and appeared uniformly round or oval. In both these groups AgNORs exhibited a type I pattern of distribution. However, as discussed earlier, in pyogenic granuloma the AgNOR dots were more in number (which is related to its proliferative activity) and slightly smaller in size compared to normal mucosa, thus signifying an inverse relationship between AgNOR number and size as reported previously. [37]

On comparing the normal mucosa with the premalignant group, there were noticeable differences in the appearance of the individual dots. AgNOR dots in the premalignant group comprised of mixed type I and type II patterns of distribution and were not uniformly round or oval as in normal mucosa. They were of slightly different shapes and sizes. Reports of an increased occurrence of irregularly shaped and bizarre AgNORs with advancing cell atypia are also available, [38] confirming the present findings. The occurrence of bizarre shaped AgNORs increased in frequency in the malignant group (comprising well-differentiated and moderately differentiated SCC), reaching the maximum in case of moderately differentiated SCC. In the malignant lesions, AgNORs were of both large and small size and their abnormal aggregation had resulted in significant AgNOR pleomorphism, with atypical appearances like the signet ring or spidery web appearance, or oblong or linear patterns. In addition, squamous cell carcinomas exhibited a predominantly type III pattern, with AgNORs distributed throughout the nucleus. Although not many studies on oral lesions are available to make any valid comparison, studies carried out on other parts of the body [20],[39],[40] do corroborate our present findings.

The present study points to the significance of the qualitative changes rather than the quantitative changes as a diagnostic indicator for premalignant/malignant lesions. When the study was originally designed, the intention was to assess the AgNOR into the three categories of distribution, viz, type I, II, and III. However, while assessing their shape and size, we observed that almost all cancer and precancer cases showed bizarre or abnormal shapes of AgNORs (pleomorphic AgNORs), with the carcinoma group exhibiting a greater percentage of such changes. Being a standard finding in all these cases, it appears that the occurrence of AgNOR pleomorphism is a true reflection of the underlying tissue changes. In a normal resting cell, where about 20 AgNOR particles can be expected, they get aggregated into one or two globules. It is possible that in malignancy, characterized by abnormal and atypical cellular proliferation, there is an alteration in their aggregation pattern, resulting in all the possible morphological variations that we have observed. A few studies have reported such abnormal profiles of AgNOR occurring in carcinomas. [32],[38] One such study [38] suggested that abnormal and bizarre AgNORs can be used as a preneoplastic marker. The available reports and the findings of the present study thus confirm that AgNOR pleomorphism is a reliable criterion in defining and differentiating between malignant and premalignant lesions. However, standardization of the AgNOR parameters and the application of image analysis can help us to precisely define AgNOR characteristics, reduce subjective errors, and increase the accuracy and reliability of future studies.


   Conclusion Top


On the basis of the present investigation, it appears that AgNORs - silver stained nucleolar organizer regions - which stain for NOR-associated proteins act as markers of both cell proliferation and malignancy. Their quantity in terms of number of AgNORs per nucleus is strictly a marker of proliferative activity of the cell. On the other hand, their qualitative profile, based on their size, shape, and pattern of distribution act as a marker of premalignant/malignant change. Increase in the abnormal size and shape of AgNORs is observed as a lesion progresses to malignancy. More than the quantitative, it is the qualitative characteristics that are more important in assessing cellular changes occurring in premalignant and malignant lesions and in distinguishing them from the normal. The present findings, especially on the AgNOR pleomorphism, may be considered preliminary. Further studies on larger samples are required to confirm this association of AgNOR quality to malignancy.

 
   References Top

1.Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the cell. Garland Publishing Inc: New York; 1983. p. 424-6. (Quoted by Smith and Crocker [4] )  Back to cited text no. 1    
2.NORs: A new method for the pathologist. Lancet 1987;1:1413-4.  Back to cited text no. 2    
3.Dervan PA, Gilmartin LG, Loftus BM, Carney DN. Argyrophilic nucleolar organizer region counts correlate with Ki67 scores. Am J Clin Pathol 1989;92:401-7.  Back to cited text no. 3  [PUBMED]  
4.Smith R, Crocker J. Evaluation of nucleolar organizer region-associated proteins in breast malignancy. Histopathology 1988;12:113-25.  Back to cited text no. 4  [PUBMED]  
5.Morgan DW, Crocker J, Watts A, Shenoi PM. Salivary gland tumours studied by means of the AgNOR technique. Histopathology 1988;13:553-9.  Back to cited text no. 5  [PUBMED]  
6.Van Heerden WF, Raubenheimer EJ. Evaluation of the nucleolar organizer region associated proteins in minor salivary gland tumors. J Oral Pathol Med 1991;20:291-5.  Back to cited text no. 6  [PUBMED]  
7.Leek RD, Alison MR, Sarraf CE. Variations in the occurrence of silver staining nucleolar organizer regions (AgNORs) in non-proliferating and proliferating tissues. J Pathol 1991;165:43-51.  Back to cited text no. 7  [PUBMED]  
8.Fallowfield ME, Cook MG. The value of nucleolar organizer region staining in the differential diagnosis of borderline melanocytic lesions. Histopathology 1989;14:299-304.  Back to cited text no. 8  [PUBMED]  
9.Howat AJ, Giri DD, Wright AL, Underwood JC. Silver-stained nucleoli and nucleolar organizer region counts are of no prognostic value in thick cutaneous malignant melanoma. J Pathol 1988;156:227-32.  Back to cited text no. 9  [PUBMED]  
10.Griffiths AP, Butler CW, Roberts P, Dixon MF, Quirke P. Silver-stained structures (AgNORs), their dependence on tissue fixation and absence of prognostic relevance in rectal adenocarcinoma. J Pathol 1989;159:121-7.  Back to cited text no. 10  [PUBMED]  
11.Coleman HG, Altini M, Groeneveld HT. Nucleolar organizer regions (AgNORs) in odontogenic cysts and ameloblastomas. J Oral Pathol Med 1996;25:436-40.  Back to cited text no. 11  [PUBMED]  
12.Crocker J, Nar P. Nucleolar organizer regions in lymphomas. J Pathol 1987;151:111-8.  Back to cited text no. 12  [PUBMED]  
13.Warnakulasuriya KA, Johnson NW. Nucleolar organiser region (NOR) distribution as a diagnostic marker in oral keratosis, dysplasia and squamous cell carcinoma. J Oral Pathol Med 1993;22:77-81.  Back to cited text no. 13  [PUBMED]  
14.Korkolopoulou P, Christodoulou P, Papanikolaou A, Thomas-Tsagli E. Proliferating cell nuclear antigen and nucleolar organizer regions in CNS tumors: Correlation with histological type and tumor grade. Am J Surg Pathol 1993;17:912-9.  Back to cited text no. 14  [PUBMED]  
15.Martins C, Carvalho YR, do Carmo MA. Argyrophilic nucleolar organizer regions (AgNORs) in odontogenic myxoma (OM) and ameloblastic fibroma (AF). J Oral Pathol Med 2001;30:489-93.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Mesquita RA, Sousa SC, Araujo NS. Proliferative activity in peripheral ossifying fibroma and ossifying fibroma. J Oral Pathol Med 1998;27:64-7.  Back to cited text no. 16    
17.Aoki K, Sakamoto M, Hirohashi S. Nucleolar organizer regions in small nodular lesions representing early stages of human hepatocarcinogenesis. Cancer 1994;73:289-93.  Back to cited text no. 17  [PUBMED]  
18.Chomette GP, Auriol MM, Labrousse F, Vaillant JM. Mucoepidermoid tumors of salivary glands: Histoprognostic value of NORs stained with AgNOR technique. J Oral Pathol Med 1991;20:130-2.  Back to cited text no. 18  [PUBMED]  
19.Moran K, Cooke T, Forster G, Gillen P, Sheehan S, Dervan P, et al . Prognostic value of nucleolar organizer regions and ploidy values in advanced colorectal cancer. Br J Surg 1989;76:1152-5.  Back to cited text no. 19  [PUBMED]  
20.Ofner D, Totsch M, Sandbichler P, Hallbrucker CH, Margreiter R, Mikuz G, et al . Silver stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer. J Pathol 1990;162:43-9.  Back to cited text no. 20    
21.Shiro T, Seki T, Naitoh Y, Inoue K, Okamura A. A correlation of argyrophilic nucleolar organizer regions with stages of hepatocellular carcinoma. Cancer 1993;71:44-9.  Back to cited text no. 21  [PUBMED]  
22.Tuccari G, Abbona GC, Giuffre G, Papotti M, Gasparri G, Barresi G, et al . AgNOR quantity as a prognostic tool in hyperplastic and neoplastic parathyroid glands. Virchows Arch 2000;437:298-303.  Back to cited text no. 22    
23.Crocker J, Ayres JG, Skilbeck NQ. Evaluation of the AgNOR technique in the diagnosis of malignant mesotheliomas. J Pathol 1988;154:23-9.  Back to cited text no. 23    
24.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;26:664-7.  Back to cited text no. 24    
25.Eslami B, Yaghmaei M, Firoozi M, Saffar AS. Nucleolar organizer regions in selected odontogenic lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:187-92.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26.Whitaker SB, Vigneswaran N, Budnick SD, Waldron CA. Giant cell lesions of the jaws: Evaluation of nucleolar organizer regions in lesions of varying behavior. J Oral Pathol Med 1993;22:402-5.  Back to cited text no. 26  [PUBMED]  
27.Rajendran R, Nair SM. Silver-binding nucleolar organizer region proteins as a possible prognostic indicator in oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1992;74:481-6.  Back to cited text no. 27  [PUBMED]  
28.Schwint AE, Savino TM, Lanfranchi HE, Marschoff E, Cabrini RL, Itoiz ME. Nucleolar organizer regions in lining epithelium adjacent to squamous cell carcinoma of human oral mucosa. Cancer 1994;73:2674-9.  Back to cited text no. 28  [PUBMED]  
29.Schwint AE, Folco A, Morales A, Cabrini RL, Itoiz ME. AgNOR mark epithelial foci in malignant transformation in hamster cheek pouch carcinogenesis. J Oral Pathol Med 1996;25:20-4.  Back to cited text no. 29  [PUBMED]  
30.Pillai KR, Sujathan K, Madhavan J, Abraham EK. Significance of silver-stained nucleolar organizer regions in early diagnosis and prognosis of oral squamous cell carcinoma: A multivariate analysis. In Vivo 2005;19:807-12  Back to cited text no. 30  [PUBMED]  
31.Nakamura M, Sano K, Kitagawa Y, Ogasawara T, Nishizawa S, Yonekura Y. Diagnostic significance of FDG-PET and argyrophilic nucleolar organizer regions (AgNORs) in oral squamous cell carcinoma. Oral Oncol 2004;40:190-8  Back to cited text no. 31  [PUBMED]  [FULLTEXT]
32.de Rosa I, Staibano S, Lo Muzio L, Delfino M, Lucariello A, Coppola A, et al . Potentially malignant and malignant lesions of the lip: Role of silver staining nucleolar organizer regions, proliferating cell nuclear antigen, p53 and c-myc in differentiation and prognosis. J Oral Pathol Med 1999;28:252-8.  Back to cited text no. 32  [PUBMED]  
33.Trere D, Pession A, Derenzini M. The silver-stained proteins of interphasic nucleolar organizer regions as a parameter of cell duplication rate. Exp Cell Res 1989;184:131-7.  Back to cited text no. 33    
34.Jan-Mohamed RM, Armstrong SJ, Crocker J, Leyland MJ, Hulten MA. The relationship between number of interphase NORs and NOR-bearing chromosomes in non-Hodgkin's lymphoma. J Pathol 1989;158:3-7.  Back to cited text no. 34  [PUBMED]  
35.Nanomura A, Mizukami Y, Oda M, Shimizu J, Watanabe Y, Kamimura R, et al . Demonstration of nucleolar organizer regions in lung carcinoma by silver staining. Surg Today 1993;23:486-90.  Back to cited text no. 35    
36.Chatterjee R, Mukhopadhyay D, Chakraborty RN, Mitra BR. Evaluation of argyrophilic nucleolar organizer regions (AgNORs) in oral carcinomas in relation to human papillomavirus infection and cytokinetics. J Oral Pathol Med 1997;26:310-4.  Back to cited text no. 36    
37.Crocker J, Egan MJ. Correlation between NOR sizes and numbers in non-Hodgkin's lymphomas. J Pathol 1988;156:233-9.  Back to cited text no. 37  [PUBMED]  
38.Yoshimi N, Gimenez-Conti IB, Slaga TJ. Morphological changes of the nucleolar organizer regions induced by 7,12 dimethylbenz[a]anthracene in the hamster cheek pouch. J Oral Pathol Med 1993;22:97-100.  Back to cited text no. 38  [PUBMED]  
39.Evans AT, Orrell JM, Grant A. Re-evaluating silver-stained nucleolar organizer regions (AgNORs) in problematic cutaneous melanocytic lesions: A study with quantitation and pattern analysis. J Pathol 1991;165:61-7.  Back to cited text no. 39  [PUBMED]  
40.De Rosa G, Staibano S, Barra E, Zeppa P, Salvatore G, Vetrani A, et al . Nucleolar organizer regions in aggressive and nonaggressive basal cell carcinoma of the skin. Cancer 1992;69:123-6.  Back to cited text no. 40  [PUBMED]  

Top
Correspondence Address:
T Elangovan
Department of Oral and Maxillofacial Pathology, Sri. Ramachandra Dental College and Hospital, Sri. Ramachandra University, Porur, Chennai - 600 116, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.40469

Rights and Permissions


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
 
 
    Tables

  [Table - 1], [Table - 2]

This article has been cited by
1 Identification of AgNORs and cytopathological changes in oral lichen planus lesions
Stefânia Jeronimo Ferreira,Maria Ângela Naval Machado,Antônio Adilson Soares de Lima,Aline Cristina Batista Rodrigues Johann,Ana Maria Trindade Grégio,Luciana Reis Azevedo-Alanis
Acta Histochemica. 2017; 119(1): 32
[Pubmed] | [DOI]
2 Identification of AgNORs and cytopathological changes in oral lichen planus lesions
Stefânia Jeronimo Ferreira,Maria Ângela Naval Machado,Antônio Adilson Soares de Lima,Aline Cristina Batista Rodrigues Johann,Ana Maria Trindade Grégio,Luciana Reis Azevedo-Alanis
Acta Histochemica. 2017; 119(1): 32
[Pubmed] | [DOI]
3 The case report on cutaneous myxoma or invasive myxomatosis in Blackfin sea catfish (Arius jella Day, 1877)
Vijayapoopathi Singaravel,Ayyaru Gopalakrishnan,Ramalingam Vijayakumar,Kuzhanthaivel Raja
Comparative Clinical Pathology. 2016; 25(2): 491
[Pubmed] | [DOI]
4 The case report on cutaneous myxoma or invasive myxomatosis in Blackfin sea catfish (Arius jella Day, 1877)
Vijayapoopathi Singaravel,Ayyaru Gopalakrishnan,Ramalingam Vijayakumar,Kuzhanthaivel Raja
Comparative Clinical Pathology. 2016; 25(2): 491
[Pubmed] | [DOI]
5 The hamster cheek pouch model for field cancerization studies
Andrea Monti-Hughes,Romina F. Aromando,Miguel A. Pérez,Amanda E. Schwint,Maria E. Itoiz
Periodontology 2000. 2015; 67(1): 292
[Pubmed] | [DOI]
6 Evaluation of AgNORs in Oral Potentially Malignant Lesions
Karin Berria Tomazelli,Filipe Modolo,Elena Riet Correa Rivero
Journal of Oncology. 2015; 2015: 1
[Pubmed] | [DOI]
7 Evaluation of AgNORs in Oral Potentially Malignant Lesions
Karin Berria Tomazelli,Filipe Modolo,Elena Riet Correa Rivero
Journal of Oncology. 2015; 2015: 1
[Pubmed] | [DOI]
8 Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques
Ignacio Gonzalez Segura,Dante Secchi,Andres Carrica,Rosario Barello,Dario Arbelo,Adriana Burgos,Mabel Brunotto,Ana M. Zarate
Journal of Oral Pathology & Medicine. 2015; 44(3): 178
[Pubmed] | [DOI]
9 Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques
Ignacio Gonzalez Segura,Dante Secchi,Andres Carrica,Rosario Barello,Dario Arbelo,Adriana Burgos,Mabel Brunotto,Ana M. Zarate
Journal of Oral Pathology & Medicine. 2015; 44(3): 178
[Pubmed] | [DOI]
10 Reduction of the argyrophilic nucleolar organizing region associated protein synthesis with age in buccal epithelial cells of healthy individuals
Burak Selvi,Halil Demirtas,Recep Eroz,Nalan Imamoglu
Aging Clinical and Experimental Research. 2015; 27(2): 201
[Pubmed] | [DOI]
11 Reduction of the argyrophilic nucleolar organizing region associated protein synthesis with age in buccal epithelial cells of healthy individuals
Burak Selvi,Halil Demirtas,Recep Eroz,Nalan Imamoglu
Aging Clinical and Experimental Research. 2015; 27(2): 201
[Pubmed] | [DOI]
12 Correlation of changes of (non)exfoliated endometrial organelles and expressions of Musashi-1 and ß-catenin with endometriosis in menstrual period
Cong-Xiang Yu,Jing-Hui Song,Lei Liang
Gynecological Endocrinology. 2014; : 1
[Pubmed] | [DOI]
13 Evaluation of Proliferation Activity in Dysplastic and Nondysplastic Oral Lichen Planus Through the Analysis of Argyrophilic Nucleolar Organizer Regions
Zohreh Jaafari-Ashkavandi,Farzaneh-Sadat Fatemi
Journal of Craniofacial Surgery. 2013; 24(3): 788
[Pubmed] | [DOI]
14 Evaluation of proliferation activity in dysplastic and nondysplastic oral lichen planus through the analysis of argyrophilic nucleolar organizer regions
Jaafari-Ashkavandi, Z. and Fatemi, F.-S.
Journal of Craniofacial Surgery. 2013; 24(3): 788-791
[Pubmed]
15 Role of multiparameter analysis of AgNORs in FNA smears of thyroid swellings in differentiating benign and malignant lesions
Hossain, M.I. and Hassan, M.Q. and Bhattacharjee, P. and Ahamad, M.S.U. and Rahman, Z.
Pathology Research International. 2012; 2012(908106)
[Pubmed]
16 Role of Multiparameter Analysis of AgNORs in FNA Smears of Thyroid Swellings in Differentiating Benign and Malignant Lesions
Mohammad Ismail Hossain,Md Quamrul Hassan,Pradip Bhattacharjee,M. Shahab Uddin Ahamad,Zillur Rahman
Pathology Research International. 2012; 2012: 1
[Pubmed] | [DOI]
17 Role of Multiparameter Analysis of AgNORs in FNA Smears of Thyroid Swellings in Differentiating Benign and Malignant Lesions
Mohammad Ismail Hossain,Md Quamrul Hassan,Pradip Bhattacharjee,M. Shahab Uddin Ahamad,Zillur Rahman
Pathology Research International. 2012; 2012: 1
[Pubmed] | [DOI]
18 Quantitative analysis of AgNOR proteins in buccal epithelial cells of Indian street boys addicted to gasp ‘golden glue’
Nandan Kumar Mondal, Sreenita Ghosh, Manas Ranjan Ray
Experimental and Toxicologic Pathology. 2011; 63(7-8): 677
[VIEW] | [DOI]
19 Oral leukoplakias with different degrees of dysplasia: comparative study of hMLH1, p53, and AgNOR : hMLH1, p53, and AgNOR in oral leukoplakia
Patrícia Carlos Caldeira, Maria Cássia Ferreira Aguiar, Ricardo Alves Mesquita, Maria Auxiliadora Vieira do Carmo
Journal of Oral Pathology and Medicine. 2011; 40(4): 305
[VIEW] | [DOI]
20 Fluorophilia: Fluorophore-containing compounds adhere non-specifically to injured neurons
Bridget E. Hawkins, Christopher J. Frederickson, Douglas S. DeWitt, Donald S. Prough
Brain Research. 2011;
[VIEW] | [DOI]
21 Quantitative analysis of AgNOR proteins in buccal epithelial cells of Indian street boys addicted to gasp ægolden glueæ
Mondal, N.K. and Ghosh, S. and Ray, M.R.
Experimental and Toxicologic Pathology. 2011; 63(7-8): 677-681
[Pubmed]
22 The role of silver staining nucleolar organiser regions (AgNORs) in lesions of the oral cavity
Gulia, S.P. and Sitaramam, E. and Reddy, K.P.
Journal of Clinical and Diagnostic Research. 2011; 5(5): 1011-1015
[Pubmed]
23 Quantitative and qualitative analysis of argyrophilic nuclear organizer regions in follicular cyst, keratocystic odontogenic tumor and ameloblastoma
Seifi, S. and Shafigh, E. and Allaie, A.
Journal of Cancer Research and Therapeutics. 2011; 7(3): 280-285
[Pubmed]
24 Oral leukoplakias with different degrees of dysplasia: Comparative study of hMLH1, p53, and AgNOR
Caldeira, P.C. and Aguiar, M.C.F. and Mesquita, R.A. and do Carmo, M.A.V.
Journal of Oral Pathology and Medicine. 2011; 40(4): 305-311
[Pubmed]
25 Upregulation of AgNOR expression in epithelial cells and neutrophils in the airways and leukocytes in peripheral blood of women chronically exposed to biomass smoke
Mondal, N.K., Das, D., Mukherjee, B., Ray, M.R.
Analytical and Quantitative Cytology and Histology. 2011; 33(1): 50-59
[Pubmed]
26 Detection of nucleoproteins in squamous cell carcinoma, and dysplastic and normal mucosa in the oral cavity by methyl green-pyronin staining
Nooshin Mohtasham,Nasser Mahdavi-Shahri,Jahanshah Salehinejad,Hamid Ejtehadi,Moluk Torabi-Parizi,Narges Ghazi
Journal of Oral Science. 2010; 52(2): 239
[Pubmed] | [DOI]
27 Detection of nucleoproteins in squamous cell carcinoma, and dysplastic and normal mucosa in the oral cavity by methyl green-pyronin staining
Nooshin Mohtasham,Nasser Mahdavi-Shahri,Jahanshah Salehinejad,Hamid Ejtehadi,Moluk Torabi-Parizi,Narges Ghazi
Journal of Oral Science. 2010; 52(2): 239
[Pubmed] | [DOI]
28 Comparison of Ki67 and modified AgNOR in dysplastic epithelial lesion, primary squamous cell carcinoma and metastatic squamous cell carcinoma of head and neck
Ashraf, M.J. and Azarpira, N. and Safarzadegan, Z. and Tadbir, A.A. and Khademi, B.
Basic and Applied Pathology. 2010; 3(4): 121-125
[Pubmed]
29 Nucleolar organizing regions and α-smooth muscle actin expression in a case of ameloblastic carcinoma
Kamath, K.P. and Vidya, M. and Shetty, N. and Karkera, B.V. and Jogi, H.
Head and Neck Pathology. 2010; 4(2): 157-162
[Pubmed]
30 Nucleolar Organizing Regions and α-Smooth Muscle Actin Expression in a Case of Ameloblastic Carcinoma
Kavitha P. Kamath, M. Vidya, Nandaprasad Shetty, Bhavana V. Karkera, Hemanth Jogi
Head and Neck Pathology. 2010; 4(2): 157
[VIEW] | [DOI]
31 Comparison of Ki67 and modified AgNOR in dysplastic epithelial lesion, primary squamous cell carcinoma and metastatic squamous cell carcinoma of head and neck
Mohamad Javad Ashraf,Negar Azarpira,Zahra Safarzadegan,Azadeh Andisheh Tadbir,Bighan Khademi
Basic and Applied Pathology. 2010; 3(4): 121
[Pubmed] | [DOI]
32 AgNOR technique could be useful for differential diagnosis of squamous carcinomatous cells and atypical cells related to human papillomavirus in cervical smears
L Palaoro,A Rocher
Biotechnic & Histochemistry. 2009; 84(3): 73
[Pubmed] | [DOI]
33 AgNOR technique could be useful for differential diagnosis of squamous carcinomatous cells and atypical cells related to human papillomavirus in cervical smears
L Palaoro,A Rocher
Biotechnic & Histochemistry. 2009; 84(3): 73
[Pubmed] | [DOI]
34 AgNOR technique could be useful for differential diagnosis of squamous carcinomatous cells and atypical cells related to human papillomavirus in cervical smears
Palaoro, L. and Rocher, A.
Biotechnic and Histochemistry. 2009; 84(3): 73-78
[Pubmed]
35 Size and number of silver-stained nucleolar organizer regions and survival rate in patients with intraoral carcinomas [Veličina i broj argirofilnih nukleolarnih organizatora i stopa preživljavanja bolesnika sa intraoralnim karcinomima]
Pešić, Z. and Mihailović, D. and Dordević, B. and Petrović, S. and Krasić, D. and Mijović, Ž. and Vučković, I.
Acta Facultatis Medicae Naissensis. 2009; 26(4): 181-185
[Pubmed]
36 Effect of indoor air pollution from biomass fuel use on argyrophilic nuclear organizer regions in buccal epithelial cells
Mondal, N.K., Dutta, A., Banerjee, A., Chakraborty, S., Lahiri, T., Ray, M.R.
Journal of Environmental Pathology, Toxicology and Oncology. 2009; 28(3): 253-259
[Pubmed]
37 Comparative analysis of cell proliferation ratio in oral lichen planus, epithelial dysplasia and oral squamous cell carcinoma
De Sousa, F.-A.-C.-G., Paradella, T.-C., Carvalho, Y.-R., Rosa, L.-E.-B.
Medicina Oral, Patologia Oral y Cirugia Bucal. 2009; 14(11): e563-e567
[Pubmed]



 

Top
 
 
  Search
 
 
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


    Abstract
    Materials and Me...
    Results
    Discussion
    Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed5592    
    Printed130    
    Emailed6    
    PDF Downloaded925    
    Comments [Add]    
    Cited by others 37    

Recommend this journal