Journal of Oral and Maxillofacial Surgery
Volume 67, Issue 7 , Pages 1432-1441 , July 2009

Prognostic Significance of p27Kip1, Ki-67, and CRTC1-MAML2 Fusion Transcript in Mucoepidermoid Carcinoma: A Molecular and Clinicopathologic Study of 101 Cases

  • Satoru Miyabe, DMD, PhD

      Affiliations

    • Research Fellow, Department of Pathology, Nagoya City University Graduate School of Medical Sciences and Research Fellow, Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan
    • ,
  • Mitsukuni Okabe, DMD, PhD

      Affiliations

    • Research Fellow, Department of Pathology, and Lecturer, Department of Oral and Maxillofacial Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    • ,
  • Hitoshi Nagatsuka, DMD, PhD

      Affiliations

    • Professor, Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    • ,
  • Yasuhisa Hasegawa, MD, PhD

      Affiliations

    • Head, Department of Head and Neck Surgery, Aichi Cancer Center Central Hospital, Nagoya, Japan
    • ,
  • Akira Inagaki, MD, PhD

      Affiliations

    • Lecturer, Department of Neuro-otolaryngology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    • Corresponding Author InformationAddress correspondence and reprint requests to Dr Inagaki: Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan
    • ,
  • Kei Ijichi, MD, PhD

      Affiliations

    • Lecturer, Department of Neuro-otolaryngology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    • ,
  • Noriyuki Nagai, DMD, PhD

      Affiliations

    • Professor Emeritus, Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    • ,
  • Tadaaki Eimoto, MD, PhD

      Affiliations

    • Professor Emeritus, Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    • ,
  • Motoo Yokoi, DMD, PhD

      Affiliations

    • Professor, Department of Oral and Maxillofacial Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    • ,
  • Kazuo Shimozato, DMD, PhD

      Affiliations

    • Professor, Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan
    • ,
  • Hiroshi Inagaki, MD, PhD

      Affiliations

    • Professor, Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

References 

  1. Goode RK, El-Naggar AK. Mucoepidermoid carcinoma. In:  Barnes L,  Eveson J,  Reichart P,  Sidransky D editor. Pathology and Genetics of Head and Neck Tumours (World Health Organization Classification of Tumours). Lyon: IARC Press; 2005;p. 219–220
  2. Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell. 1994;78:67
  3. Polyak K, Kato JY, Solomon MJ, et al. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 1994;8:9
  4. Polyak K, Lee MH, Erdjument-Bromage H, et al. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell. 1994;78:59
  5. Lloyd RV, Erickson LA, Jin L, et al. p27Kip1: A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol. 1999;154:313
  6. Gerdes J, Schwab U, Lemke H, et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13
  7. Gerdes J. Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. Semin Cancer Biol. 1990;1:199
  8. Pires FR, de Almeida OP, de Araújo VC, et al. Prognostic factors in head and neck mucoepidermoid carcinoma. Arch Otolaryngol Head Neck Surg. 2004;174:130;174
  9. Tonon G, Modi S, Wu L, et al. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Nat Genet. 2003;33:208
  10. Enlund F, Behboudi A, Andren Y, et al. Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors. Exp Cell Res. 2004;292:21
  11. Wu L, Liu J, Gao P, et al. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. EMBO J. 2005;24:2391
  12. Coxon A, Rozenblum E, Park YS, et al. Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes. Cancer Res. 2005;65:7137
  13. Conkright MD, Canettieri G, Screaton R, et al. TORCs: Transducers of regulated CREB activity. Mol Cell. 2003;12:413
  14. Iourgenko V, Zhang W, Mickanin C, et al. Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. Proc Natl Acad Sci USA. 2003;100:12147
  15. Wu L, Aster JC, Blacklow SC, et al. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet. 2000;26:484
  16. Okabe M, Miyabe S, Nagatsuka H, et al. MECT1-MAML2 fusion transcript defines a favorable subset of mucoepidermoid carcinoma. Clin Cancer Res. 2006;12:3902
  17. Auclair PL, Goode RK, Ellis GL. Mucoepidermoid carcinoma of intraoral salivary glands: Evaluation and application of grading criteria in 143 cases. Cancer. 1992;69:2021
  18. Goode RK, Auclair PL, Ellis GL. Mucoepidermoid carcinoma of the major salivary glands: Clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer. 1998;82:1217
  19. Guzzo M, Andreola S, Sirizzotti G, et al. Mucoepidermoid carcinoma of the salivary glands: Clinicopathologic review of 108 patients treated at the National Cancer Institute of Milan. Ann Surg Oncol. 2002;9:688
  20. Okabe M, Inagaki H, Murase T, et al. Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland. Mod Pathol. 2001;14:1008
  21. Inagaki H, Okabe M, Seto M, et al. API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma: Multiplex RT-PCR detection using formalin-fixed paraffin-embedded specimens. Am J Pathol. 2001;158:699
  22. Choi CS, Choi G, Jung KY, et al. Low expression of p27(Kip1) in advanced mucoepidermoid carcinomas of head and neck. Head Neck. 2001;23:292
  23. Handra-Luca A, Ruhin B, Lesty C, et al. p27, SKP2, and extra-cellular signal-related kinase signaling in human salivary gland mucoepidermoid carcinoma. Oral Oncol. 2006;42:1005
  24. Troncone G, Fulciniti F, Zeppa P, et al. Cyclin-dependent kinase inhibitor p27(Kip1) expression in thyroid cells obtained by fine-needle aspiration biopsy: A preliminary report. Diagn Cytopathol. 2000;23:77
  25. Troncone G, Migliaccio I, Caleo A, et al. p27(Kip1) expression and grading of breast cancer diagnosed on cytological samples. Diagn Cytopathol. 2004;30:375
  26. Behboudi A, Enlund F, Winnes M, et al. Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene. Genes Chromosomes Cancer. 2006;45:470
  27. Tirado Y, Williams MD, Hanna EY, et al. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: Implications for histogenesis and biologic behavior. Genes Chromosomes Cancer. 2007;46:708
  28. Kaye FJ. Emerging biology of malignant salivary gland tumors offers new insights into the classification and treatment of mucoepidermoid cancer. Clin Cancer Res. 2006;12:3878
  29. El-Naggar AK, Lovell M, Killary AM, et al. A mucoepidermoid carcinoma of minor salivary gland with t(11;19)(q21;p13.1) as the only karyotypic abnormality. Cancer Genet Cytogenet. 1996;87:29
  30. Fehr A, Röser K, Heidorn K, et al. A new type of MAML2 fusion in mucoepidermoid carcinoma. Genes Chromosomes Cancer. 2008;47:203
  31. Brandwein MS, Ivanov K, Wallace DI, et al. Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol. 2001;25:835
  32. In:  Jaffe ES,  Harris NL,  Stein H, et al. editor. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues (World Health Organization Classification of Tumours). Lyon: IARC Press; 2001;
  33. Komiya T, Park Y, Modi S, et al. Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Oncogene. 2006;25:6128
  34. le Sage C, Nagel R, Egan DA, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007;26:3699
  35. Galardi S, Mercatelli N, Giorda E, et al. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem. 2007;282:23716

PII: S0278-2391(09)00311-5

doi: 10.1016/j.joms.2009.03.021

Journal of Oral and Maxillofacial Surgery
Volume 67, Issue 7 , Pages 1432-1441 , July 2009

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