EXPRESSION OF MCM3 AND KI-67 AS DIAGNOSTIC MARKERS IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS | ||
| Alexandria Dental Journal | ||
| Article 17, Volume 40, Issue 2, December 2015, Pages 248-255 PDF (1.53 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/adjalexu.2015.59161 | ||
| Authors | ||
| RM Abdalla* ; MH El Abany* ; OR Ramadan* ; M.A Habib* | ||
| Masters student of Oral Pathology, Faculty of Dentistry-Alexandria University | ||
| Abstract | ||
| Introduction: Salivary gland tumors (SGTs) may represent a considerable diagnostic challenge, primarily because of the complexity of the classification and the rarity of several entities. Since proliferative activity is a reliable method to assess tumor biology. There has been continuous research to find such biological markers. Ki-67 is a widely accepted proliferation marker, with its expression tightly associated with the cell cycle. It is implicated in many of human cancers as a prognostic factor. MCM-3, member of minichromosome maintenance proteins family, is upregulated in proliferating cells. MCM-3 overexpression in almost all human cancers implicates that it might facilitate the tumorigenesis by playing a role in the malignant transformation of cells. Objectives: to evaluate the MCM-3 protein expression in benign and malignant salivary gland tumors and compare the obtained results with the expression of Ki-67 proliferation antigen. Materials and methods: Immunohistochemical analysis of 20 cases of SGTs with 2 sections from each specimen (20 sections for antiKi- 67antibody and 20 sections for antiMCM3antibody) and 5 control cases. Immunohistochemical staining was performed using a Labeled Strept- Avidin Biotin method (LSAB). Results: Normal salivary gland tissue showed negative immunoreactivity for both Ki-67 and MCM-3 in epithelial and myoepithelial cells. All the examined cases showed positive expression for both proliferative markers in benign and malignant SGTs, with different intensities. Conclusions: The proliferative markers Ki-67 and MCM-3 proteins are overexpressed in malignant salivary gland tumors, than benign ones. Both Ki-67 and MCM-3 may be reliably applied as diagnostic markers to distinguish benign from malignant salivary gland tumors. | ||
| Keywords | ||
| Salivary gland tumor; Immunohistochemistry; MCM-3; Ki-67 | ||
| References | ||
|
1. Nagao T, Sato E, Inoue R, Oshiro H, Reisuke H. Takahashi, Takeshi Nagai,. Immunohistochemical Analysis of Salivary Gland Tumors: Application for Surgical Pathology Practice. Acta Histochem Cytochem 2012; 45: 269-82.
2. Brandwein MS, Ferlito A, Bradley PJ, Hille JJ, Rinaldo A. Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol 2002; 122: 758- 64.
3. Seifert G, Donath K. Hybrid tumours of salivary glands. Definition and classification of five rare cases. Eur J Cancer B Oral Oncol 1996; 32B: 251-9.
4. Habberstad AH, Gulati S, Torp SH. Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisom erase IIα in human anaplastic astrocytomas - an immunohistochemical study. Diagn Pathol 2011; 6: 43-50.
5. Brown DC, Gatter KC. Ki67 protein: the immaculate deception? Histopathology 2002; 40: 2-11.
6. van Dierendonck JH, Keijzer R, van de Velde CJ, Cornelisse CJ. Nuclear distribution of the Ki-67 antigen during the cell cycle: Comparison with growth fraction in human breast cancer cells. Cancer Res 1989; 49: 2999-3006.
7. Huret JL. Rhabdoid predisposition syndrome. Atlas Genet Cytogenet Oncol Haematol. 2000. Available at: http://AtlasGeneticsOncology. org/Kprones/rhabdKpronID10051.html
8. Hua C, Zhao G, Li Y, Bie L. Minichromosome Maintenance (MCM) Family as potential diagnostic and prognostic tumor markers for human gliomas. BMC Cancer 2014; 14: 526 -33.
9. Scott IS, Morris LS, Bird K, Davies RJ, Vowler SL, Rushbrook SM, et al. A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer. J Pathol 2003; 201: 187- 97.
10. Chong JP, Thommes P, Blow JJ. The role of MCM/P1proteins in the licensing of DNA replication. Trends Biochem Sci 1996; 21: 102-6.
11. Aparicio OM, Weinstein DM, Bell SP. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell 1997; 91: 59-69.
12. Thommes P, Fett R, Schray B, Burkhart R, Barnes M, Kennedy C, et al. Properties of the nuclear P1 protein, a mammalian homologue of the yeast MCM3 replication protein. Nucleic Acids Res 1992; 20: 1069- 74.
13.Burkhart R, Schulte D, Musahl C, Göhring F, Knippers R. Interactions of human nuclear proteins P1Mcm3 and P1Cdc46. Eur J Biochem 1995; 228: 431-8.
14.Musahl C, Holthoff HP, Lesch R, Knippers R. Stability of the replicative Mcm3 protein in proliferating and differentiating human cells. Exp Cell Res 1998; 24: 260-4.
15.Hennessy KM, Clark CD, Botstein D. Subcellular localization of yeast CDC46 varies with the cell cycle. Genes Dev 1990; 4: 2252-63.
16.Yan H, Merchant M, Tye BK. Cell cycle-regulated nuclearlocalization of MCM2 and MCM 3, which are required for the initiation ofDNA synthesis at chromosomal replication origins in yeast. Genes Dev 1993; 7: 2149-60.
17.Crook T, Wrede D, Tidy JA, Mason WP, Evans DJ, Vousden KH. Clonal p53 mutation in primary cervical cancer: association with human-papillomavirusnegative tumours. Lancet 1992; 339: 1070-3.
18.Busby-Earle RM, Steel CM, Williams AR, Cohen B, Bird CC p53 mutations in cervical carcinogenesis-low frequency and lack of correlation with human papillomavirus status. Br J Cancer 1994; 69: 732-7.
19.Ha SA, Shin SM, Namkoong H, Lee H, Cho GW, et al. Cancer-Associated Expression of Minichromosome Maintenance 3 Gene in Several Human Cancers and Its Involvement in Tumorigenesis. Clin Cancer Res 2004; 10: 8386-95.
20.Ben-Izhak O, Akrish S, Nagler RM. Ki67 and salivary cancer. Cancer Invest 2008; 26: 1015-23.
21.Ashkavandi ZJ, Najvani AD, Tadbir AA, Pardis S, Ranjbar MA, Ashraf MJ. MCM3 as a novel diagnostic marker in benign and malignant salivary gland tumors. Asian Pac J Cancer Prev 2013; 14: 3479-82.
22.Barnes L, Eveson J, Reichart P, Sidransky D. Tumors of the salivary glands. In: World Health Organization classification of tumors. Pathology and genetics of head and neck tumors. Lyon: IARC, 2005. p 210-81.
23.Quinn CM, Wright NA. The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables. J Pathol 1990; 160: 93-102.
24.Tadbir AA, Pardis S, Ashkavandi ZJ, Najvani AD, Ashraf MJ, Taheri A, et al. Expression of Ki67 and CD105 as proliferation and angiogenesis markers in salivary gland tumors. Asian Pac J Cancer Prev 2012; 13: 5155-9.
25.Trandafirescu M, Cotuțiu C, Cojocaru E, Foia L. Immunohistochemical Aspects In Pleomorphic Adenoma, Related To Its Histogenesis And Malignization. Romanian J Oral Rehabil 2012; 4: 11-6.
26. Freitas LL, Araujo VC, Martins MT, Chone C, Crespo A, Altemani A. Biomarker analysis in carcinoma ex pleomorphic adenoma at an early phase of carcinomatous transformation. Int J Surg Pathol 2005; 13: 337-42.
27.Sangeetha N, Palaniappan V, Hemavathy N, Subathra K. Histo-pathological Analysis of Salivary Gland Lesions with Ki-67 Immunoprofile. RJPBCS 2014; 5: 993-1004.
28.Nguyen LH, Black MJ, Hier M, Chauvin P, Rochon L. HER2/neu and Ki-67 as Prognostic Indicators in Mucoepidermoid Carcinoma of Salivary Glands. J Otolaryngol 2003; 32: 328-31.
29.Expression of proliferating cell nucler antigen and ki67 antigen in mucoepidermoid carcinoma. The lobal journal of medicine and hygiene, 2013.
30.Lazzaro B, Cleveland D. P53 and Ki-67 antigen expression in small oral biopsy specimens of salivary gland tumors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 89: 613-7.
31.Fonseca I, Felix A, Soares J. Cell proliferationin salivary gland adenocarcinomas with myoepithelial participation. Astudy of 78 cases. Virchows Arch 1997; 430: 227-32.
32.Vargas PA, Cheng Y, Barrett AW, Craig GT, Speight PM .Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumoursJ Oral Pathol Med 2008; 37: 309-18.
33.Fanshawe T, Prevost A, Sainsbury R, Williams G, Stoeber K. DNA replication licensing and cell cycle kinetics of normal and neoplastic breast. Brit J Cancer 2005; 93: 1295-300.
34.Ghazy SE, Helmy IM, Baghdadi HM. Maspin and MCM2 immunoprofiling in salivary gland carcinomas Diagn Pathol 2011; 6: 89.
35.Yamaguchi N, Ito E, Azuma S, Honma R, Yanagisawa Y, Nishikawa A, et al. Fox A1 as a lineage-specific oncogene in luminal type breast cancer. Biochem Biophys Res Commun 2008; 365: 711-7.
36. Söling A, Sackewitz M, Volkmar M, Schaarschmidt D, Jacob R, Holzhausen HJ, et al. Minichromosome Maintenance Protein 3 Elicits a Cancer-Restricted Immune Response in Patients with Brain Malignancies and Is a Strong Independent Predictor of Survival in Patients with Anaplastic Astrocytoma Clin Cancer Res 2005; 11: 249-58.
37.Constantinos G, Stephanie V, Philippe V, Stamatios T. MCM proteins as diagnostic and prognostic tumor marker in the clinical setting. Histol Histopathol 2010; 25: 351-70.
38.Shetty A, Loddo M, Fanshawe T, Prevost AT, Sainsbury R, Williams GH, et al. DNAreplication licensing and cell cycle kinetics of normal andneoplastic breast. Br J Cancer 2005; 11: 1295-300.
39.Lee YS, Ha SA, Kim HJ, Shin SM, Kim HK, Kim S, et al. Minichromosome maintenance protein 3 is a candidate proliferation marker in papillary thyroid carcinoma. Exp Mol Pathol 2010; 88: 138-42.
| ||
|
Statistics Article View: 181 PDF Download: 615 |
||
