Molecular Heterogeneity in Mucoepidermoid Carcinoma: Conceptual and Practical Implications

Head and Neck Pathology - Tập 7 - Trang 23-27 - 2013
Diana Bell1, Adel K. El-Naggar1
1Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.

Tóm tắt

Mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy of the upper aerodigestive tract and tracheobronchial tree, is also known for its considerable cellular heterogeneity including epidermoid, intermediate and mucin producing cells. Despite this structural and cellular heterogeneity, MEC is uniquely characterized by a specific translocation t(11; 19) (q12; p13), resulting in a fusion between the MECT1 and the MAML2 genes. Although the incidence of this fusion in MEC varies, it is generally accepted that more than 50 % of this entity manifest the MECT1-MAML2. Fusion-positive cases showed significantly better survival than fusion-negative cases, suggesting that MECT1-MAML2 represents a specific prognostic molecular marker in MEC. We contend that fusion in MEC represents a distinct mechanism in the development of this entity. In that context, fusion positive MEC, regardless of grade, manifest a more stable genome and better clinical behaviour, while fusion negative MEC represent a distinctly different pathway characterized by marked genomic instability and relatively aggressive tumors.

Tài liệu tham khảo

Seethala RR. An update on grading of salivary gland carcinomas. Head Neck Pathol. 2009;3(1):69–77. Seethala RR, Dacic S, Cieply K, Kelly LM, Nikiforova MN. A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. Am J Surg Pathol. 2010;34(8):1106–21. Brenner JC, Chinnaiyan AM. Translocations in epithelial cancers. Biochim Biophys Acta. 2009;1796(2):201–15. Nordkvist A, Gustafsson H, Juberg-Ode M, Stenman G. Recurrent rearrangements of 11q14-22 in mucoepidermoid carcinoma. Cancer Genet Cytogenet. 1994;74(2):77–83. Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA. 2009;106(44):18740–4. Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, Perez-Ordonez B, Have C, Asa SL, Leong IT, Bradley G, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50(7):559–70. Skalova A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, Starek I, Geierova M, Simpson RH, Passador-Santos F, Ryska A, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34(5):599–608. Stenman G. Fusion oncogenes and tumor type specificity–insights from salivary gland tumors. Semin Cancer Biol. 2005;15(3):224–35. Stenman G, Andersson MK, Andren Y. New tricks from an old oncogene: gene fusion and copy number alterations of MYB in human cancer. Cell Cycle. 2010;9(15):2986–95. El-Naggar AK, Lovell M, Killary AM, Clayman GL, Batsakis JG. A mucoepidermoid carcinoma of minor salivary gland with t(11; 19)(q21; p13.1) as the only karyotypic abnormality. Cancer Genet Cytogenet. 1996;87(1):29–33. Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, O’Neil K, Stover K, El-Naggar A, Griffin JD, Kirsch IR, 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(2):208–13. Iourgenko V, Zhang W, Mickanin C, Daly I, Jiang C, Hexham JM, Orth AP, Miraglia L, Meltzer J, Garza D, Chirn GW, 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(21):12147–52. Anzick SL, Chen WD, Park Y, Meltzer P, Bell D, El-Naggar AK, Kaye FJ. Unfavorable prognosis of CRTC1-MAML2 positive mucoepidermoid tumors with CDKN2A deletions. Genes Chromosomes Cancer. 2010;49(1):59–69. Komiya T, Park Y, Modi S, Coxon AB, Oh H, Kaye FJ. Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Oncogene. 2006;25(45):6128–32. Jaskoll T, Htet K, Abichaker G, Kaye FJ, Melnick M. CRTC1 expression during normal and abnormal salivary gland development supports a precursor cell origin for mucoepidermoid cancer. Gene Expr Patterns. 2011;11(1–2):57–63. Behboudi A, Enlund F, Winnes M, Andren Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, Makitie A, Grenman R, Mark J, et al. Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene. Genes Chromosomes Cancer. 2006;45(5):470–81. Tirado Y, Williams MD, Hanna EY, Kaye FJ, Batsakis JG, El-Naggar AK. 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(7):708–15. Fehr A, Roser K, Heidorn K, Hallas C, Loning T, Bullerdiek J. A new type of MAML2 fusion in mucoepidermoid carcinoma. Genes Chromosomes Cancer. 2008;47(3):203–6. Nakayama T, Miyabe S, Okabe M, Sakuma H, Ijichi K, Hasegawa Y, Nagatsuka H, Shimozato K, Inagaki H. Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. Mod Pathol. 2009;22(12):1575–81. Jee KJ, Persson M, Heikinheimo K, Passador-Santos F, Aro K, Knuutila S, Odell EW, Makitie A, Sundelin K, Stenman G, Leivo I. Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma. Mod Pathol. 2013;26(2):213–22. Luna MA. Salivary mucoepidermoid carcinoma: revisited. Adv Anat Pathol. 2006;13(6):293–307. O’Neill ID. Gefitinib as targeted therapy for mucoepidermoid carcinoma of the lung: possible significance of CRTC1-MAML2 oncogene. Lung Cancer. 2009;64(1):129–30. Han SW, Kim HP, Jeon YK, Oh DY, Lee SH, Kim DW, Im SA, Chung DH, Heo DS, Bang YJ, Kim TY. Mucoepidermoid carcinoma of lung: potential target of EGFR-directed treatment. Lung Cancer. 2008;61(1):30–4. Rossi G, Sartori G, Cavazza A, Tamberi S. Mucoepidermoid carcinoma of the lung, response to EGFR inhibitors, EGFR and K-RAS mutations, and differential diagnosis. Lung Cancer. 2009;63(1):159–60.