Skip to main content

Molecular Characterization of Salivary Gland Carcinomas

  • 474 Accesses

Abstract

The recently updated WHO classification of head and neck tumors has listed more than 20 (sub-)types of salivary gland cancers. Although there was a consensus of the Board that diagnosis on histological criteria alone may be inaccurate, the editors finally reasoned that the necessary setup for molecular analyses is not globally available, as yet, or the data are either not convincing or robust enough to supplement the histological and immunohistochemical diagnostic tools. Nevertheless, the increasing knowledge about tumor-type-specific translocations, point mutations, and amplifications in salivary gland cancers needs more explanatory comments than the new WHO fascicle could afford, particularly taking into account the already established molecular support of diagnostic and predictive pathology in specialized clinical centers. In the German Salivary Gland Expert Network (www.hansepathnet.de), we advocate the application of molecular analyses for clinicopathological purposes in mucoepidermoid, adenoid cystic, and secretory carcinomas, while more translational research is necessary before molecular tools can be applied in other neoplasias covered in this chapter, in routine clinical practice.

Keywords

  • Biomarker
  • CRTC1-MAML2
  • ERBB2
  • ETV6-NTRK3
  • EWSR1-ATF1
  • Fusion oncogene
  • HMGA2
  • Mutation
  • MYB-NFIB
  • PRKD1
  • Salivary gland cancer

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-030-02958-6_2
  • Chapter length: 16 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   109.00
Price excludes VAT (USA)
  • ISBN: 978-3-030-02958-6
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Hardcover Book
USD   149.99
Price excludes VAT (USA)
Fig. 2.1
Fig. 2.2
Fig. 2.3

Abbreviations

a.k.a.:

Also known as

ACC:

Acinic cell carcinoma

AdCC:

Adenoid cystic carcinoma

AR:

Androgen receptor

CAMSG:

Cribriform adenocarcinoma of minor salivary glands

CREB:

cAMP response element-binding protein

CXPA:

Carcinoma ex pleomorphic adenoma

FGF-IGF-PI3K:

Fibroblast growth factor-insulin-like growth factor-phosphatidylinositol 3-kinase pathway

FISH:

Fluorescence in situ hybridization

HCCC:

Hyalinizing clear-cell carcinoma

IDC:

Low-grade intraductal carcinoma

MAPK:

Mitogen-activated protein kinase

MASC:

Mammary analogue secretory carcinoma

MEC:

Mucoepidermoid carcinoma

NOS:

Not otherwise specified

PA:

Pleomorphic adenoma

PAC:

Polymorphous adenocarcinoma

PI3K:

Phosphatidylinositol 3-kinase

RT-PCR:

Reverse transcription polymerase chain reaction

SC:

Secretory breast carcinoma

SDC:

Salivary duct carcinoma

SGC:

Salivary gland carcinomas

References

  1. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. Pathology and genetics of head and neck tumours. World Health Organization Classification of Tumours. 4th ed. Lyon: IARC Press; 2017.

    Google Scholar 

  2. 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.

    CrossRef  CAS  PubMed  Google Scholar 

  3. 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.

    CrossRef  CAS  PubMed  Google Scholar 

  4. Behboudi A, Enlund F, Winnes M, Andren Y, Nordkvist A, Leivo I, et al. Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene. Genes Chromosomes Cancer. 2006;45(5):470–81.

    CrossRef  CAS  PubMed  Google Scholar 

  5. Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, 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.

    CrossRef  CAS  PubMed  Google Scholar 

  6. Fehr A, Meyer A, Heidorn K, Röser K, Löning T, Bullerdiek J. A link between the expression of the stem cell marker HMGA2, grading, and the fusion CRTC1-MAML2 in mucoepidermoid carcinoma. Genes Chromosomes Cancer. 2009;48(9):777–85.

    CrossRef  CAS  PubMed  Google Scholar 

  7. Verdorfer I, Fehr A, Bullerdiek J, Scholz N, Brunner A, Krugmann J, et al. Chromosomal imbalances, 11q21 rearrangement and MECT1-MAML2 fusion transcript in mucoepidermoid carcinomas of the salivary gland. Oncol Rep. 2009;22(2):305–11.

    CAS  PubMed  Google Scholar 

  8. Möller E, Stenman G, Mandahl N, Hamberg H, Molne L, van den Oord JJ, et al. POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. J Pathol. 2008;215(1):78–86.

    CrossRef  CAS  PubMed  Google Scholar 

  9. Di Renzo F, Doneda L, Menegola E, Sardella M, De Vecchi G, Collini P, et al. The murine Pou6f2 gene is temporally and spatially regulated during kidney embryogenesis and its human homolog is overexpressed in a subset of Wilms tumors. J Pediatr Hematol Oncol. 2006;28(12):791–7.

    CrossRef  PubMed  Google Scholar 

  10. Nakano T, Yamamoto H, Hashimoto K, Tamiya S, Shiratsuchi H, Nakashima T, et al. HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status. Histopathology. 2013;63(3):378–92.

    CrossRef  PubMed  Google Scholar 

  11. Rao PH, Roberts D, Zhao Y-J, Bell D, Harris CP, Weber RS, et al. Deletion of 1p32-p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands. Clin Cancer Res. 2008;14(16):5181–7.

    CrossRef  CAS  PubMed  Google Scholar 

  12. Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS, et al. Whole exome sequencing of adenoid cystic carcinoma. J Clin Invest. 2013;123(7):2965–8.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mitani Y, Liu B, Rao PH, Borra VJ, Zafereo M, Weber RS, et al. Novel MYBL1 gene rearrangements with recurrent MYBL1-NFIB fusions in salivary adenoid cystic carcinomas lacking t(6;9) translocations. Clin Cancer Res. 2015;22(3):725–33.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  14. Stenman G, Persson F, Andersson MK. Diagnostic and therapeutic implications of new molecular biomarkers in salivary gland cancers. Oral Oncol. 2014;50(8):683–90.

    CrossRef  CAS  PubMed  Google Scholar 

  15. Lannon CL, Sorensen PH. ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages. Semin Cancer Biol. 2005;15(3):215–23.

    CrossRef  CAS  PubMed  Google Scholar 

  16. Ito Y, Ishibashi K, Masaki A, Fujii K, Fujiyoshi Y, Hattori H, et al. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion. Am J Surg Pathol. 2015;39(5):602–10.

    CrossRef  PubMed  Google Scholar 

  17. Weinreb I. Hyalinizing clear cell carcinoma of salivary gland: a review and update. Head Neck Pathol. 2013;7(Suppl 1):S20–9.

    CrossRef  PubMed  Google Scholar 

  18. Shah AA, LeGallo RD, van Zante A, Frierson HF Jr, Mills SE, Berean KW, et al. EWSR1 genetic rearrangements in salivary gland tumors: a specific and very common feature of hyalinizing clear cell carcinoma. Am J Surg Pathol. 2013;37(4):571–8.

    CrossRef  PubMed  Google Scholar 

  19. Dooley AL, Winslow MM, Chiang DY, Banerji S, Stransky N, Dayton TL, et al. Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev. 2011;25(14):1470–5.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32(6):596–604.

    CrossRef  CAS  PubMed  Google Scholar 

  21. Sharon E, Kelly R, Szabo E. Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine. Head Neck Oncol. 2010;2(1):12.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  22. Skalova A, Sima R, Kaspirkova-Nemcova J, Simpson RH, Elmberger G, Leivo I, et al. Cribriform adenocarcinoma of minor salivary gland origin principally affecting the tongue: characterization of new entity. Am J Surg Pathol. 2011;35(8):1168–76.

    CrossRef  PubMed  Google Scholar 

  23. Ihrler S, Weiler C, Hirschmann A, Sendelhofert A, Lang S, Guntinas-Lichius O, et al. Intraductal carcinoma is the precursor of carcinoma ex pleomorphic adenoma and is often associated with dysfunctional p53. Histopathology. 2007;51(3):362–71.

    CrossRef  CAS  PubMed  Google Scholar 

  24. Jordan R, Dardick I, Lui E, Birek C. Demonstration of c-erbB-2 oncogene overexpression in salivary gland neoplasms by in situ hybridization. J Oral Pathol Med. 1994;23(5):226–31.

    CrossRef  CAS  PubMed  Google Scholar 

  25. Diegel CR, Cho KR, El-Naggar AK, Williams BO, Lindvall C. Mammalian target of rapamycin-dependent acinar cell neoplasia after inactivation of Apc and Pten in the mouse salivary gland: implications for human acinic cell carcinoma. Cancer Res. 2010;70(22):9143–52.

    CrossRef  CAS  PubMed  Google Scholar 

  26. Chan RC, Chan JY. Head and neck mucoepidermoid carcinoma: a curious association with second primary malignancy. Otolaryngol Head Neck Surg. 2014;151(5):797–801.

    CrossRef  PubMed  Google Scholar 

  27. Wolfish EB, Nelson BL, Thompson LD. Sinonasal tract mucoepidermoid carcinoma: a clinicopathologic and immunophenotypic study of 19 cases combined with a comprehensive review of the literature. Head Neck Pathol. 2012;6(2):191–207.

    CrossRef  PubMed  Google Scholar 

  28. Fonseca FP, de Andrade BA, Lopes MA, Pontes HA, Vargas PA, de Almeida OP. P63 expression in papillary cystadenoma and mucoepidermoid carcinoma of minor salivary glands. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(1):79–86.

    CrossRef  PubMed  Google Scholar 

  29. Lennerz JK, Perry A, Mills JC, Huettner PC, Pfeifer JD. Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion. Am J Surg Pathol. 2009;33(6):835–43.

    CrossRef  PubMed  Google Scholar 

  30. Pires FR, de Almeida OP, de Araujo VC, Kowalski LP. Prognostic factors in head and neck mucoepidermoid carcinoma. Arch Otolaryngol Head Neck Surg. 2004;130(2):174–80.

    CrossRef  PubMed  Google Scholar 

  31. Fehr A, Röser K, Heidorn K, Hallas C, Löning T, Bullerdiek J. A new type of MAML2 fusion in mucoepidermoid carcinoma. Genes Chromosomes Cancer. 2008;47(3):203–6.

    CrossRef  CAS  PubMed  Google Scholar 

  32. Enlund F, Behboudi A, Andren Y, Oberg C, Lendahl U, Mark J, 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(1):21–8.

    CrossRef  CAS  PubMed  Google Scholar 

  33. Coxon A, Rozenblum E, Park YS, Joshi N, Tsurutani J, Dennis PA, et al. Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes. Cancer Res. 2005;65(16):7137–44.

    CrossRef  CAS  PubMed  Google Scholar 

  34. Wu L, Liu J, Gao P, Nakamura M, Cao Y, Shen H, et al. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. EMBO J. 2005;24(13):2391–402.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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.

    CrossRef  PubMed  Google Scholar 

  36. Jee KJ, Persson M, Heikinheimo K, Passador-Santos F, Aro K, Knuutila S, et al. Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma. Mod Pathol. 2013;26(2):213–22.

    CrossRef  CAS  PubMed  Google Scholar 

  37. Nakayama T, Miyabe S, Okabe M, Sakuma H, Ijichi K, Hasegawa Y, et al. Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. Mod Pathol. 2009;22(12):1575–81.

    CrossRef  CAS  PubMed  Google Scholar 

  38. Seethala RR, Chiosea SI. MAML2 status in mucoepidermoid carcinoma can no longer be considered a prognostic marker. Am J Surg Pathol. 2016;40(8):1151–3.

    CrossRef  PubMed  Google Scholar 

  39. Behboudi A, Winnes M, Gorunova L, van den Oord JJ, Mertens F, Enlund F, et al. Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)-associated TORC1-MAML2 gene fusion. Genes Chromosomes Cancer. 2005;43(2):202–5.

    CrossRef  CAS  PubMed  Google Scholar 

  40. 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.

    CrossRef  CAS  PubMed  Google Scholar 

  41. Fehr A, Röser K, Belge G, Löning T, Bullerdiek J. A closer look at Warthin tumors and the t(11;19). Cancer Genet Cytogenet. 2008;180(2):135–9.

    CrossRef  CAS  PubMed  Google Scholar 

  42. Anzick SL, Chen WD, Park Y, Meltzer P, Bell D, El-Naggar AK, et al. Unfavorable prognosis of CRTC1-MAML2 positive mucoepidermoid tumors with CDKN2A deletions. Genes Chromosomes Cancer. 2009;49(1):59–69.

    CrossRef  CAS  Google Scholar 

  43. Kang H, Tan M, Bishop JA, Jones S, Sausen M, Ha PK, Agrawal N, et al. Whole-exome sequencing of salivary gland mucoepidermoid carcinoma. Clin Cancer Res. 2017;23(1):283–8.

    CrossRef  CAS  PubMed  Google Scholar 

  44. Besch R, Berking C. POU transcription factors in melanocytes and melanoma. Eur J Cell Biol. 2014;93(1–2):55–60.

    CrossRef  CAS  PubMed  Google Scholar 

  45. Perotti D, De Vecchi G, Testi MA, Lualdi E, Modena P, Mondini P, et al. Germline mutations of the POU6F2 gene in Wilms tumors with loss of heterozygosity on chromosome 7p14. Hum Mutat. 2004;24(5):400–7.

    CrossRef  CAS  PubMed  Google Scholar 

  46. Yoo J, Robinson RA. H-ras gene mutations in salivary gland mucoepidermoid carcinomas. Cancer. 2000;88(3):518–23.

    CrossRef  CAS  PubMed  Google Scholar 

  47. Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol. 2011;12(8):815–24.

    CrossRef  CAS  PubMed  Google Scholar 

  48. Persson M, Andren Y, Moskaluk CA, Frierson HF Jr, Cooke SL, Futreal PA, et al. Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma. Genes Chromosomes Cancer. 2012;51(8):805–17.

    CrossRef  CAS  PubMed  Google Scholar 

  49. 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 U S A. 2009;106(44):18740–4.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  50. Ramsay RG, Gonda TJ. MYB function in normal and cancer cells. Nat Rev Cancer. 2008;8(7):523–34.

    CrossRef  CAS  PubMed  Google Scholar 

  51. von Holstein SL, Fehr A, Persson M, Nickelsen M, Therkildsen MH, Prause JU, et al. Lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma: genomic profiles, gene fusions, and clinical characteristics. Ophthalmology. 2014;121(5):1125–33.

    CrossRef  Google Scholar 

  52. Drier Y, Cotton MJ, Williamson KE, Gillespie SM, Ryan RJ, Kluk MJ, et al. An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet. 2016;48(3):265–72.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N, et al. The mutational landscape of adenoid cystic carcinoma. Nat Genet. 2013;45(7):791–8.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  54. Brayer KJ, Frerich CA, Kang H, Ness SA. Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 2016;6(2):176–87.

    CrossRef  CAS  PubMed  Google Scholar 

  55. Brill LB 2nd, Kanner WA, Fehr A, Andrén Y, Moskaluk CA, Löning T, et al. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24(9):1169–76.

    CrossRef  CAS  PubMed  Google Scholar 

  56. Skálová A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, 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.

    PubMed  Google Scholar 

  57. Fehr A, Löning T, Stenman G. Mammary analogue secretory carcinoma of the salivary glands with ETV6-NTRK3 gene fusion. Am J Surg Pathol. 2011;35(10):1600–2.

    CrossRef  PubMed  Google Scholar 

  58. Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002;2(5):367–76.

    CrossRef  CAS  PubMed  Google Scholar 

  59. Skalova A, Vanecek T, Majewska H, Laco J, Grossmann P, Simpson RH, et al. Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, beta-catenin, EGFR, and CCND1 genes. Am J Surg Pathol. 2014;38(1):23–33.

    CrossRef  PubMed  Google Scholar 

  60. Skalova A, Vanecek T, Simpson RH, Laco J, Majewska H, Baneckova M, et al. Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 ETV6 gene rearranged tumors with lack of detection of classical ETV6-NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion. Am J Surg Pathol. 2016;40(1):3–13.

    CrossRef  PubMed  Google Scholar 

  61. Rubin BP, Chen CJ, Morgan TW, Xiao S, Grier HE, Kozakewich HP, et al. Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol. 1998;153(5):1451–8.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  62. Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet. 1998;18(2):184–7.

    CrossRef  CAS  PubMed  Google Scholar 

  63. Kralik JM, Kranewitter W, Boesmueller H, Marschon R, Tschurtschenthaler G, Rumpold H, et al. Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia. Diagn Pathol. 2011;6:19.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  64. Griffith C, Seethala R, Chiosea SI. Mammary analogue secretory carcinoma: a new twist to the diagnostic dilemma of zymogen granule poor acinic cell carcinoma. Virchows Arch. 2011;459(1):117–8.

    CrossRef  PubMed  Google Scholar 

  65. Connor A, Perez-Ordonez B, Shago M, Skalova A, Weinreb I. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity. Am J Surg Pathol. 2012;36(1):27–34.

    CrossRef  PubMed  Google Scholar 

  66. Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61(3):387–94.

    CrossRef  PubMed  Google Scholar 

  67. Pinto A, Nose V, Rojas C, Fan YS, Gomez-Fernandez C. Searching for mammary analogue secretory carcinoma of salivary gland among its mimics. Mod Pathol. 2014;27(1):30–7.

    CrossRef  CAS  PubMed  Google Scholar 

  68. Bishop JA, Yonescu R, Batista D, Eisele DW, Westra WH. Most nonparotid “acinic cell carcinomas” represent mammary analog secretory carcinomas. Am J Surg Pathol. 2013;37(7):1053–7.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  69. Solar AA, Schmidt BL, Jordan RC. Hyalinizing clear cell carcinoma: case series and comprehensive review of the literature. Cancer. 2009;115(1):75–83.

    CrossRef  PubMed  Google Scholar 

  70. Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, 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):559–7.

    CrossRef  CAS  PubMed  Google Scholar 

  71. Bilodeau EA, Weinreb I, Antonescu CR, Zhang L, Dacic S, Muller S, et al. Clear cell odontogenic carcinomas show EWSR1 rearrangements: a novel finding and a biological link to salivary clear cell carcinomas. Am J Surg Pathol. 2013;37(7):1001–5.

    CrossRef  PubMed  Google Scholar 

  72. Jin R, Craddock KJ, Irish JC, Perez-Ordonez B, Weinreb I. Recurrent hyalinizing clear cell carcinoma of the base of tongue with high-grade transformation and EWSR1 gene rearrangement by FISH. Head Neck Pathol. 2012;6(3):389–94.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  73. Persson F, Andrén Y, Winnes M, Wedell B, Nordkvist A, Gudnadottir G, et al. High-resolution genomic profiling of adenomas and carcinomas of the salivary glands reveals amplification, rearrangement, and fusion of HMGA2. Genes Chromosomes Cancer. 2009;48(1):69–82.

    CrossRef  CAS  PubMed  Google Scholar 

  74. Queimado L, Lopes CS, Reis AM. WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors. Genes Chromosomes Cancer. 2007;46(3):215–25.

    CrossRef  CAS  PubMed  Google Scholar 

  75. Roijer E, Nordkvist A, Strom AK, Ryd W, Behrendt M, Bullerdiek J, et al. Translocation, deletion/amplification, and expression of HMGIC and MDM2 in a carcinoma ex pleomorphic adenoma. Am J Pathol. 2002;160(2):433–40.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  76. Stenman G. Fusion oncogenes in salivary gland tumors: molecular and clinical consequences. Head Neck Pathol. 2013;7(Suppl 1):S12–9.

    CrossRef  PubMed  Google Scholar 

  77. Nordkvist A, Roijer E, Bang G, Gustafsson H, Behrendt M, Ryd W, et al. Expression and mutation patterns of p53 in benign and malignant salivary gland tumors. Int J Oncol. 2000;16(3):477–83.

    CAS  PubMed  Google Scholar 

  78. Jaehne M, Roeser K, Jaekel T, Schepers JD, Albert N, Loning T. Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer. 2005;103(12):2526–33.

    CrossRef  PubMed  Google Scholar 

  79. Jaspers HC, Verbist BM, Schoffelen R, Mattijssen V, Slootweg PJ, van der Graaf WT, et al. Androgen receptor-positive salivary duct carcinoma: a disease entity with promising new treatment options. J Clin Oncol. 2011;29(16):e473–6.

    CrossRef  PubMed  Google Scholar 

  80. Dalin MG, Desrichard A, Katabi N, Makarov V, Walsh LA, Lee KW, et al. Comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to apocrine breast cancer. Clin Cancer Res. 2016;22(18):4623–33.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  81. Andersson MK, Stenman G. The landscape of gene fusions and somatic mutations in salivary gland neoplasms - implications for diagnosis and therapy. Oral Oncol. 2016;57:63–9.

    CrossRef  CAS  PubMed  Google Scholar 

  82. Simpson RH. Salivary duct carcinoma: new developments--morphological variants including pure in situ high grade lesions; proposed molecular classification. Head Neck Pathol. 2013;7(Suppl 1):S48–58.

    CrossRef  PubMed  Google Scholar 

  83. Mitani Y, Rao PH, Maity SN, Lee YC, Ferrarotto R, Post JC, et al. Alterations associated with androgen receptor gene activation in salivary duct carcinoma of both sexes: potential therapeutic ramifications. Clin Cancer Res. 2014;20(24):6570–81.

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kuo YJ, Weinreb I, Perez-Ordonez B. Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature. Head Neck Pathol. 2013;7(Suppl 1):S59–67.

    CrossRef  PubMed  Google Scholar 

  85. Delgado R, Klimstra D, Albores-Saavedra J. Low grade salivary duct carcinoma. A distinctive variant with a low grade histology and a predominant intraductal growth pattern. Cancer. 1996;78(5):958–67.

    CrossRef  CAS  PubMed  Google Scholar 

  86. Brandwein-Gensler M, Hille J, Wang BY, Urken M, Gordon R, Wang LJ, et al. Low-grade salivary duct carcinoma: description of 16 cases. Am J Surg Pathol. 2004;28(8):1040–4.

    CrossRef  PubMed  Google Scholar 

  87. Stevens TM, Kovalovsky AO, Velosa C, Shi Q, Dai Q, Owen RP, et al. Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study. Mod Pathol. 2015;28(8):1084–100.

    CrossRef  CAS  PubMed  Google Scholar 

  88. Weinreb I, Tabanda-Lichauco R, Van der Kwast T, Perez-Ordonez B. Low-grade intraductal carcinoma of salivary gland: report of 3 cases with marked apocrine differentiation. Am J Surg Pathol. 2006;30(8):1014–21.

    CrossRef  PubMed  Google Scholar 

  89. Abrams AM, Cornyn J, Scofield HH, Hansen LS. Acinic cell adenocarcinoma of the major salivary glands. A clinicopathologic study of 77 cases. Cancer. 1965;18:1145–62.

    CrossRef  CAS  PubMed  Google Scholar 

  90. Ellis GL, Auclair PL. Tumors of the salivary glands, AFIP atlas of tumor pathology. 4th ed. Washington, D.C.: American Registry of Pathology; 2008.

    Google Scholar 

  91. Chiosea SI, Griffith C, Assaad A, Seethala RR. The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. Am J Surg Pathol. 2012;36(3):343–50.

    CrossRef  PubMed  Google Scholar 

  92. Mitelmann F, Johansson B, Mertens F, editors. Mitelman database of chromosome aberrations and gene fusions in cancer; 2016. Available from: http://cgap.nci.nih.gov/Chromosomes/Mitelman.

  93. Clauditz TS, Gontarewicz A, Lebok P, Tsourlakis MC, Grob TJ, Munscher A, et al. Epidermal growth factor receptor (EGFR) in salivary gland carcinomas: potentials as therapeutic target. Oral Oncol. 2012;48(10):991–6.

    CrossRef  CAS  PubMed  Google Scholar 

  94. Clauditz TS, Reiff M, Gravert L, Gnoss A, Tsourlakis MC, Munscher A, et al. Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas. Pathology. 2011;43(5):459–64.

    CrossRef  CAS  PubMed  Google Scholar 

  95. Ettl T, Schwarz-Furlan S, Haubner F, Muller S, Zenk J, Gosau M, et al. The PI3K/AKT/mTOR signalling pathway is active in salivary gland cancer and implies different functions and prognoses depending on cell localisation. Oral Oncol. 2012;48(9):822–30.

    CrossRef  CAS  PubMed  Google Scholar 

  96. Weinreb I, Piscuoglio S, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, et al. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet. 2014;46(11):1166–9.

    CrossRef  CAS  PubMed  Google Scholar 

  97. Weinreb I, Zhang L, Tirunagari LM, Sung YS, Chen CL, Perez-Ordonez B, et al. Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer. 2014;53(10):845–56.

    CrossRef  CAS  PubMed  Google Scholar 

  98. Majewska H, Skalova A, Weinreb I, Stodulski D, Hyrcza M, Stankiewicz C, et al. Giant cribriform adenocarcinoma of the tongue showing PRKD3 rearrangement. Pol J Pathol. 2016;67(1):84–90.

    CrossRef  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to André Fehr .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Fehr, A., Bullerdiek, J., Jaekel, T., Löning, T. (2019). Molecular Characterization of Salivary Gland Carcinomas. In: Licitra, L., Locati, L. (eds) Salivary Gland Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-02958-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-02958-6_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-02957-9

  • Online ISBN: 978-3-030-02958-6

  • eBook Packages: MedicineMedicine (R0)