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  • 1 Oral Pathology Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
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Abstract

This study was designed to correlate the expression of both MDM2 and NM23 in pleomorphic adenoma (PA) to clinical background, histological features, local recurrence, and metastatic potentiality in this tumor. Expression of MDM2 and NM23 was studied immunohistochemically in 23 cases of PA. Our results demonstrated MDM2 and NM23 overexpression in almost all cases of PA. There was a significant difference of the MDM2 and NM23 mean values between benign PA and both carcinoma-ex PA and metastasizing PA. The results of this study show that the overexpression of NM23 and MDM2 oncoproteins could be used as reliable predictors of malignant progression as well as metastatic potentiality of PA.

  • 1. G. Seifert 2005 WHO international histological classification of tumours Histological Typing of Salivary Gland Tumours Springer-Verlag Berlin 122 129.

    • Search Google Scholar
    • Export Citation
  • 2. H. Harada 2000 Histomorphological investigation regarding to malignant transformation of pleomorphic adenoma (so-called malignant mixed tumor) of salivary gland origin: special reference to carcinoma Kurume Med J 47 307 323.

    • Search Google Scholar
    • Export Citation
  • 3. D.R. Gnepp 1993 Malignant mixed tumors of the salivary glands Pathol Ann 28 279 328.

  • 4. K.D. Olsen J.E. Lewis 2001 Carcinoma ex pleomorphic adenoma: a clinicopathologic review Head Neck 23 9 705 712.

  • 5. T. Numata K. Hiruma T. Tsukuda T. Asano 2004 Malignant mixed tumor Gan To Kagaku Ryoho Mar 31 3 314 317.

  • 6. J.E. Lewis K.D. Olsen T.J. Sebo 2001 Carcinoma ex pleomorphic adenoma: Pathologic analysis of 73 cases Hum Pathol 32 596 604.

  • 7. J. Slingerland I. Tannok 1998 Cell Proliferation and Cell Death TannokHill The Basic Science of Oncology 3rd ed Mc Graw-Hill New York, USA 237 241.

    • Search Google Scholar
    • Export Citation
  • 8. H.G. Haitel Wiener U. Baethge M. Marberger M. Susani 2000 Mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters Clin Cancer Res 6 1840 1844.

    • Search Google Scholar
    • Export Citation
  • 9. C. Capoulade L.M. Mir K. Carlier Y. Lécluse C. Tétaud Z. Mishal J. Wiels 2001 Apoptosis of tumoral and non-tumoral lymphoid cells is induced by both mdm2 and p53 antisense oligodeoxynucleotides Blood 97 1043 1049.

    • Search Google Scholar
    • Export Citation
  • 10. T. Dilla J.A. Velasco D.L. Medina J.F. G Palacios P. Santisteban 2000 The mdm2 oncoprotein promotes apoptosis in p53-deficient human medullary thyroid carcinoma cells Endocrinology 141 420 429.

    • Search Google Scholar
    • Export Citation
  • 11. S.C. Evans M. Viswanathan J.M. Narayana A.K. El-Naggar G. Lozano 2001 An alternatively spliced Hdm2 product increases p53 activity by inhibiting Hdm2 Oncogene 20 4041 4049.

    • Search Google Scholar
    • Export Citation
  • 12. J.D. Weber J.R. Jeffers J.E. Rehg D. Randle G. Lozano M.F. Roussel C.J. Sherr G.P. Zambetti 2000 P53-independent functions of the p19 ARF tumor suppressor Genes Dev 14 2358 2365.

    • Search Google Scholar
    • Export Citation
  • 13. Mantesso S.V. Lourenco Loducca I. Bendit B. Garicochea F.D. Nunes V.C. de Araujo 2004 Mdm2 mRNA expression in salivary gland tumor cell lines J Oral Pathol Med 33 96 101.

    • Search Google Scholar
    • Export Citation
  • 14. T. Schlott H. Nagel R. Laskawi H. Eiffert M. Droese 2001 Genetic analysis of the human oncoprotein mdm2 in benign and malignant tumors of the salivary gland Pathobiology 69 67 76.

    • Search Google Scholar
    • Export Citation
  • 15. F.S. Leach T. Tokino P. Meltzer 1993 P35 mutation and MDM2 amplification in human soft tissue sarcomas Cancer Res 53 2231 2234.

  • 16. M.B. Moller O. Nielson N.T. Pederson 2002 Frequent alteration of MDM2 and P35 in the molecular progression of non-Hodgkin's lymphoma Histopathology 41 4 322 330.

    • Search Google Scholar
    • Export Citation
  • 17. C.J. Liu K.W. Change S.Y. Chao 2004 The molecular markers for prognostic evaluation of areca-associated buccal squamous cell carcinoma J Oral Pathol Med 33 327 334.

    • Search Google Scholar
    • Export Citation
  • 18. C. Kapitanovic T. Cacev M. Berkovic 2004 NM23-HI expression and loss of heterozygozity in colon adenocarcinoma J Clin Pathol 57 12 1312 1318.

    • Search Google Scholar
    • Export Citation
  • 19. J.M. McGregor C.C.W. Yu E.A. Dublin 1993 P35 immunoreactivity in human malignant melanoma and dysplastic naevi Br J Dermatol 128 606 611.

    • Search Google Scholar
    • Export Citation
  • 20. M. Salerno T. Quatas D. Palmierri P.S. Steeg 2003 Inhibition of signal transduction by the nm23 metastasis suppressor: possible mechanisms Clin Exp Metastasis 20 1 3 10.

    • Search Google Scholar
    • Export Citation
  • 21. M. Sarris M. Konopka C.S. Lee 2003 Differential expression of the nm23 protein in the progression of oesophageal adenocarcinoma Pathology 35 1 37 41.

    • Search Google Scholar
    • Export Citation
  • 22. A. De La Rosa R.L. Williams P.S. Steeg 1995 Nm23/nucleoside diphosphate kinase: towards a structural and biochemical understanding of its biological functions Bioessays 17 1 53 62.

    • Search Google Scholar
    • Export Citation
  • 23. W. Pan Y.X. Wang G. Li 2004 Study on the expression of nm23-M1/NDPK a during the blastocyst adhesiveness in the mouse endometrial Shi Yan Sheng Wu Xue Bao 37 4 289 294.

    • Search Google Scholar
    • Export Citation
  • 24. L. Dusonchet S. Corsale M. Migliavaca 2003 Nm23-H1 expression does not predict clinical survival in colorectal cancer patients Oncol Rep 10 5 1257 1263.

    • Search Google Scholar
    • Export Citation
  • 25. J.M. Freije N.J. MacDonald P.S. Steeg 1998 NM23 and tumor metastasis: basic and translational advances Biochem Soc Symp 63 261 271.

    • Search Google Scholar
    • Export Citation
  • 26. H. Zhao M. Jhanwar-Uniyal P.K. Datta 2004 Expression profile of genes associated with anti-metastatic gene: nm23-mediated metastasis inhibition in breast carcinoma cells Int J Cancer 109 1 65 70.

    • Search Google Scholar
    • Export Citation
  • 27. J.H. Lee X. Zhang W.Y. Jung Y.S. Chae I. Kim 2004 DNA ploidy and c-Kit mutation in gastrointestinal stromal tumors World J Gastroenterol 10 3475 3479.

    • Search Google Scholar
    • Export Citation
  • 28. S.J. Naish 1989 Handbook — Immunohistochemical Staining Methods DAKO Corporation Carpintaria.

  • 29. D.R. Gnepp 1993 Malignant mixed tumors of the salivary glands: a review Pathol Annu 28 Pt1 279 328.

  • 30. C. Magdalena G. Charles M. Nasir Bhatti C. Charles H. William 2000 Metastasizing mixed tumor of the partoid initial presentation as a solitary kidney tumor and ultimate carcinomatous transformation at the primary site Am J Surg Pathol 24 1159 1164.

    • Search Google Scholar
    • Export Citation
  • 31. M.E. Perry S.M. Mendrysa L.J. Saucedo P. Tannous M. Holubar 2000 P76MDM2 inhibits the ability of p90MDM2 to destabilize p53 J Biol Chem 275 8 5733 5738.

    • Search Google Scholar
    • Export Citation
  • 32. M. Rolfe M. Chui M. Pagano 1997 The ubiquitin-mediated proteolytic pathway as a therapeutic area J Mol Med 75 5 17.

  • 33. S. Fang J.P. Jensen R.L. Ludwig K.H. Vousden A.M. Weissman 2000 Mdm2 is a finger-dependent ubiquitin protein ligase for itself and p53 J Biol Chem 275 8945 8951.

    • Search Google Scholar
    • Export Citation
  • 34. J. Jorge F.R. Pires F.A. Alves D.E. Perez L.P. Kowalski M.A. Lopes O.P. Almeida 2002 Juvenile intraoral pleomorphic adenoma: report of five cases and review of the literature Int J Oral Maxillofac Surg 31 273 275.

    • Search Google Scholar
    • Export Citation
  • 35. Y. Yamamoto A.K. Virmani I.I. Wistuba D. McIntire F. Vuitch J. Alboressaavedra 1996 Loss of heterozygosity and microsatellite alterations in p53 and RB genes in adenoid cystic carcinoma of the salivary glands Hum Pathol 27 1204 1210.

    • Search Google Scholar
    • Export Citation
  • 36. G. Reifenberger L. Liu K. Ichimura E.E. Schmidt V.P. Collins 1993 Amplification and over-expression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations Cancer Res 54 2736 2739.

    • Search Google Scholar
    • Export Citation
  • 37. S. Pilotti G. Della Torri C. Lavarino 1997 Distinct MDM2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms J Pathol 181 14 24.

    • Search Google Scholar
    • Export Citation
  • 38. A.H. McCann A. Kirley D.N. Carney 1995 Amplification of the MDM2 gene in human breast cancer and its association with MDM2 and p53 protein status Br J Cancer 71 981 985.

    • Search Google Scholar
    • Export Citation
  • 39. V.C. de Araújo M.T. Martins K.R.M. Leite R.S. Gomez N.S. de Araújo 2000 Immunohistochemical Mdm2 expression in minor salivary gland tumours and its relationship to p53 gene status Oral Oncol 36 67 69.

    • Search Google Scholar
    • Export Citation
  • 40. B. Vogelstein D. Lane A.J. Levine 2000 Surfing the p53 network Nature 408 307 310.

  • 41. J. Roth M. Dobbelstein D.A. Freedman T. Shenk A.J. Levine 1998 Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein EMBO J 17 554 564.

    • Search Google Scholar
    • Export Citation
  • 42. M. Argentini N. Barboule B. Wasylyk 2002 The contribution of the acidic domain of Mdm2 to p53 and Mdm2 stability Oncogene 2011 1267 1275.

    • Search Google Scholar
    • Export Citation
  • 43. P. Sun P. Dong K. Dai G.J. Hannon D. Beach 1998 p53-independent role of MDM2 in TGF-beta1 resistance Science 282 2270 2272.

  • 44. R. Ranju S. Agarwal M. Mathur B. Wasylyk K. Shukla 2000 Induction of mdm2-p2 transcripts correlates with stabilized wild-type p53 in betel- and tobacco-related human oral cancer Am J Pathol 157 587 596.

    • Search Google Scholar
    • Export Citation
  • 45. B. Antonsson J.C. Martinou 2000 The Bcl-2 protein family Exp Cell Res 256 1 50 57.

  • 46. D.R. Brown C.A. Thomas S.P. Deb 1998 The human oncoprotein mdm2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis EMBO J 17 2513 2525.

    • Search Google Scholar
    • Export Citation
  • 47. J. Sjöström C. Blomqvist A. Heikkil N. Bengtsson I. Mjaaland P. Malmström B. Ostenstadt J. Bergh E. Wist V. Valvere E. Saksela 2000 Predictive value of p53, mdm-2, p21, and mib-1 for chemotherapy response in advanced breast cancer Clin Cancer Res 6 3103 3110.

    • Search Google Scholar
    • Export Citation
  • 48. P.S. Steeg L.K. Bevilacqua U.P. Thorgeirsson J.E. Talmadge L.A. Liotta M.E. Sobel 1988 Evidence for a novel gene associated with low tumor metastatic potential J Natl Cancer Inst 80 200 204.

    • Search Google Scholar
    • Export Citation
  • 49. C. Charpin C. Bouvier S. Garcia F. Martini L. Andrac M.N. Lavaut C. Allasia 1997 Automated and quantitative immunocytochemical assays of nm23/NDPK protein in breast carcinomas Int J Cancer 74 416 420.

    • Search Google Scholar
    • Export Citation
  • 50. M.T. Hartsough P.S. Steeg 2000 Nm23/nucleoside diphosphate kinase in human cancers J Bioenerg Biomembranes 32 301 308.

  • 51. T. Ouatas M. Salerno D. Palmieri P.S. Steeg 2003 Basic and translational advances in cancer metastasis: nm23 J Bioenerg Biomembranes 35 73 79.

    • Search Google Scholar
    • Export Citation
  • 52. R.P. Takes R.J. Baatenburg de Jong E. Schuuring J. Hermans A.A. Vis S.V. Litninov J.H. van Krieken 1997 Markers for assessment of nodal metastasis in laryngeal carcinoma Arch Otolaryngol Head Neck Surg 123 412 419.

    • Search Google Scholar
    • Export Citation
  • 53. Z. Fan P.J. Beresford D.Y. Oh D. Zhang J. Lieberman 2003 Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor Cell 112 659 672.

    • Search Google Scholar
    • Export Citation
  • 54. H. Jin J. Li X. Chen 1997 Significance of nm23 expression in malignant carcinoma of salivary gland Zhonghua Kouquiang Yixue Zazhi 32 341 343.

    • Search Google Scholar
    • Export Citation
  • 55. H. Shi R. He W. Qiu 1997 nm23 expression and its correlation with lung metastasis in human salivary adenoid cystic carcinoma Zhonghua Kouquiang Yixue Zazhi 32 4 6.

    • Search Google Scholar
    • Export Citation
  • 56. S. Xu M. Wu Y. Yang J. Wang Z. Chen 2001 Detection of proteins and mRNA of p16, p53, and nm23 in mucoepidermoid carcinoma of salivary glands and their prognostic significance Zhonghua Binglixue Zazhi 30 273 275.

    • Search Google Scholar
    • Export Citation
  • 57. C. Birek W. Chung K. Mcneill 1998 Heterogeneous expression of NM23-H1 putative oncossupressor-protein in salivary gland neoplasms Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86 215.

    • Search Google Scholar
    • Export Citation
  • 58. L. Gong Z.L. Chen J. Hu H.Y. Huo 2004 Expression of p16 and nm23 genes in salivary gland tumours Huaxi Kouqiang Yixue Zazhi 22 155 157.

    • Search Google Scholar
    • Export Citation
  • 59. P. Bertheau A. De La Rosa P.S. Steeg M.J. Merino 1994 NM23 protein in neoplastic and nonneoplastic thyroid tissues Am J Pathol 145 26 32.

    • Search Google Scholar
    • Export Citation
  • 60. C.S. Lee R.A. Clarke K.T. Tran J.H. Kearsley S.T. Chou 1999 nm23 protein expression and p53 immunoreactivity in cutaneous fibrohistiocytic tumors Pathology 31 123 126.

    • Search Google Scholar
    • Export Citation
  • 61. M.H. Bosnar J. Gunzburg R. Bago K. Brecevic I. Weber J. Pavelic 2004 Subcellular localization of A and B Nm23/NDPK subunits Exp Cell Res 298 275 284.

    • Search Google Scholar
    • Export Citation
  • 62. K.C. do Nascimento P.R. de Faria L.L. Dib M.C.F. de Aguiar 2006 Immunohistochemical localization of the NM23 protein in salivary gland neoplasms with distinct biological behavior Virchows Arch 449 660 666.

    • Search Google Scholar
    • Export Citation
  • 63. H. Katori A. Nozawa M. Tsukuda 2007 Increased expression of cyclooxygenase-2 and Ki-67 are associated with malignant transformation of pleomorphic adenoma Auris Nasus Larynx 34 79 84.

    • Search Google Scholar
    • Export Citation
  • 64. M.T. Martins A. Altemani L. Freitas V.C. Araújo 2005 Maspin expression in carcinoma ex pleomorphic adenoma J Clin Pathol 58 1311 1314.

    • Search Google Scholar
    • Export Citation
  • 65. V.C. de Araújo A. Altemani C. Furuse M.T. Martins N.S. de Araújo 2006 Immunoprofile of reactive salivary myoepithelial cells in intraductal areas of carcinoma ex-pleomorphic adenoma Oral Oncol 42 1011 1016.

    • Search Google Scholar
    • Export Citation

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