Abdalla, R., El Abany, M., Ramadan, O., Habib, M. (2015). EXPRESSION OF MCM3 AND KI-67 AS DIAGNOSTIC MARKERS IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS. Alexandria Dental Journal, 40(2), 248-255. doi: 10.21608/adjalexu.2015.59161
RM Abdalla; MH El Abany; OR Ramadan; M.A Habib. "EXPRESSION OF MCM3 AND KI-67 AS DIAGNOSTIC MARKERS IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS". Alexandria Dental Journal, 40, 2, 2015, 248-255. doi: 10.21608/adjalexu.2015.59161
Abdalla, R., El Abany, M., Ramadan, O., Habib, M. (2015). 'EXPRESSION OF MCM3 AND KI-67 AS DIAGNOSTIC MARKERS IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS', Alexandria Dental Journal, 40(2), pp. 248-255. doi: 10.21608/adjalexu.2015.59161
Abdalla, R., El Abany, M., Ramadan, O., Habib, M. EXPRESSION OF MCM3 AND KI-67 AS DIAGNOSTIC MARKERS IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS. Alexandria Dental Journal, 2015; 40(2): 248-255. doi: 10.21608/adjalexu.2015.59161
EXPRESSION OF MCM3 AND KI-67 AS DIAGNOSTIC MARKERS IN BENIGN AND MALIGNANT SALIVARY GLAND TUMORS
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.
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.
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.