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Expression of Mucins in Salivary Gland Mucoepidermoid Carcinoma

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Abstract

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour in both adults and children. Histological grading of MEC is subjective, but plays an important role in predicting patient prognosis. Epithelial mucin (MUC) status may aid in establishing a more accurate grade. This study aimed to investigate the expression of various mucins (MUC1, MUC2, MUC4 and MUC5AC) in MECs to determine a possible correlation with tumour grade. Fifteen cases of each tumour grade (low-, intermediate-, and high-grade) were retrieved from the pathology archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria. The patients included 23 men and 22 women, and ranged from 13 to 85 years (mean 49.8 years). Sections from formalin-fixed paraffin-embedded (FFPE) tissue were used for fluorescence in situ hybridization (FISH) for MAML2 rearrangements and MUC immunohistochemical analysis. The percentage immunohistochemical expression of the neoplastic mucous cells was evaluated first, followed by the overall percentage expression of all tumour cells. The results indicated that MUC1 overexpression may be a reliable marker of high-grade MECs, whereas MUC4 overexpression may be more indicative of low-grade tumours. MUC5AC expression was considered an unreliable marker in determining grade. MUC2 was only expressed in a single case of MEC and may be considered a useful marker to exclude MEC as a diagnostic possibility. This study demonstrates that MECs show an altered MUC expression pattern that can be used for diagnostic purposes and to aid in establishing a more accurate tumour grade.

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References

  1. Ellis GL, Auclair PL. AFIP atlas of tumor pathology. Washington, DC: American Registry of Pathology in Collaboration with the Armed Forces Institute of Pathology; 2008.

    Google Scholar 

  2. El-Naggar AK, Chan JKC, Rubin-Grandis J, Takata T, Slootweg PJ, International Agency for Research on Cancer. World Health Organization classification of tumours. 4th ed. Lyon: International Agency for Research on Cancer; 2017.

    Google Scholar 

  3. Brandwein MS, Ivanov K, Wallace DI, Hille JJ, Wang B, Fahmy A, et al. Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol. 2001;25(7):835–45.

    Article  CAS  Google Scholar 

  4. Griffith CC, Seethala RR. Mucoepidermoid carcinoma of minor salivary glands: potential pitfalls and prognostic challenges. Pathol Case Rev. 2011;16(4):145–50.

    Article  Google Scholar 

  5. Klijanienko J, El-Naggar AK, Servois V, Rodriguez J, Validire P, Vielh P. Mucoepidermoid carcinoma ex pleomorphic adenoma: nonspecific preoperative cytologic findings in six cases. Cancer. 1998;84(4):231–4.

    Article  CAS  Google Scholar 

  6. Waldron CA, Koh ML. Central mucoepidermoid carcinoma of the jaws: report of four cases with analysis of the literature and discussion of the relationship to mucoepidermoid, sialodontogenic, and glandular odontogenic cysts. J Oral Maxillofac Surg. 1990;48(8):871–7.

    Article  CAS  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. Bishop JA, Cowan ML, Shum CH, Westra WH. MAML2 rearrangements in variant forms of mucoepidermoid carcinoma: ancillary diagnostic testing for the ciliated and warthin-like variants. Am J Surg Pathol. 2018;42(1):130–6.

    Article  Google Scholar 

  9. Luk PP, Wykes J, Selinger CI, Ekmejian R, Tay J, Gao K, et al. Diagnostic and prognostic utility of Mastermind-like 2 (MAML2) gene rearrangement detection by fluorescent in situ hybridization (FISH) in mucoepidermoid carcinoma of the salivary glands. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(5):530–41.

    Article  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. 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 Chromosom Cancer. 2006;45(5):470–81.

    Article  CAS  Google Scholar 

  12. Saade RE, Bell D, Garcia J, Roberts D, Weber R. Role of CRTC1/MAML2 translocation in the prognosis and clinical outcomes of mucoepidermoid carcinoma. JAMA Otolaryngol Head Neck Surg. 2016;142(3):234–40.

    Article  Google Scholar 

  13. Luna MA. Salivary mucoepidermoid carcinoma: revisited. Adv Anat Pathol. 2006;13(6):293–307.

    Article  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. Cipriani NA, Lusardi JJ, McElherne J, Pearson AT, Olivas AD, Fitzpatrick C, et al. Mucoepidermoid carcinoma: a comparison of histologic grading systems and relationship to MAML2 rearrangement and prognosis. Am J Surg Pathol. 2019;43(7):885–97.

    Article  Google Scholar 

  16. Seethala RR. An update on grading of salivary gland carcinomas. Head Neck Pathol. 2009;3(1):69–77.

    Article  Google Scholar 

  17. 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(7):1217–24.

    Article  CAS  Google Scholar 

  18. Gemryd P, Lundquist PG, Tytor M, Hellquist HB, Nordenskjold B. Prognostic significance of DNA ploidy in mucoepidermoid carcinoma. Eur Arch Otorhinolaryngol. 1997;254(4):180–5.

    Article  CAS  Google Scholar 

  19. 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.

    Article  Google Scholar 

  20. Van Heerden WF, Raubenheimer EJ, Dreyer L. The role of DNA ploidy and Ki-67 in the grading of mucoepidermoid carcinomas. Anticancer Res. 2005;25(3c):2589–92.

    PubMed  Google Scholar 

  21. Nance MA, Seethala RR, Wang Y, Chiosea SI, Myers EN, Johnson JT, et al. Treatment and survival outcomes based on histologic grading in patients with head and neck mucoepidermoid carcinoma. Cancer. 2008;113(8):2082–9.

    Article  Google Scholar 

  22. Llupi M, Qoku R. Expression of mucins in normal salivary glands and mucoepidermoid carcinoma of salivary glands. 2013.

  23. Lau SK, Weiss LM, Chu PG. Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol. 2004;122(1):61–9.

    Article  Google Scholar 

  24. Krishn SR, Ganguly K, Kaur S, Batra SK. Ramifications of secreted mucin MUC5AC in malignant journey: a holistic view. Carcinogenesis. 2018;39(5):633–51.

    Article  CAS  Google Scholar 

  25. Alos L, Lujan B, Castillo M, Nadal A, Carreras M, Caballero M, et al. Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands. Am J Surg Pathol. 2005;29(6):806–13.

    Article  Google Scholar 

  26. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4(1):45–60.

    Article  CAS  Google Scholar 

  27. Shemirani N, Osipov V, Kolker A, Khampang P, Kerschner JE. Expression of mucin (MUC) genes in mucoepidermoid carcinoma. Laryngoscope. 2011;121(1):167–70.

    Article  CAS  Google Scholar 

  28. Speight PM, Barrett AW. Salivary gland tumours: diagnostic challenges and an update on the latest WHO classification. Diagn Histopathol. 2020;26(4):147–58.

    Article  Google Scholar 

  29. Rahn JJ, Dabbagh L, Pasdar M, Hugh JC. The importance of MUC1 cellular localization in patients with breast carcinoma: an immunohistologic study of 71 patients and review of the literature. Cancer. 2001;91(11):1973–82.

    Article  CAS  Google Scholar 

  30. Wreesmann VB, Sieczka EM, Socci ND, Hezel M, Belbin TJ, Childs G, et al. Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker. Cancer Res. 2004;64(11):3780–9.

    Article  CAS  Google Scholar 

  31. Handra-Luca A, Lamas G, Bertrand JC, Fouret P. MUC1, MUC2, MUC4, and MUC5AC expression in salivary gland mucoepidermoid carcinoma: diagnostic and prognostic implications. Am J Surg Pathol. 2005;29(7):881–9.

    Article  Google Scholar 

  32. Siyi L, Shengwen L, Min R, Wenjun Y, Lizheng W, Chenping Z. Increased expression of MUC-1 has close relation with patient survivor in high-grade salivary gland mucoepidermoid carcinoma. J Oral Pathol Med. 2014;43(8):579–84.

    Article  Google Scholar 

  33. Copin MC, Devisme L, Buisine MP, Marquette CH, Wurtz A, Aubert JP, et al. From normal respiratory mucosa to epidermoid carcinoma: expression of human mucin genes. Int J Cancer. 2000;86(2):162–8.

    Article  CAS  Google Scholar 

  34. Jepson S, Komatsu M, Haq B, Arango ME, Huang D, Carraway CA, et al. Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Oncogene. 2002;21(49):7524–32.

    Article  CAS  Google Scholar 

  35. Rachagani S, Torres MP, Moniaux N, Batra SK. Current status of mucins in the diagnosis and therapy of cancer. BioFactors. 2009;35(6):509–27.

    Article  CAS  Google Scholar 

  36. Hoshi H, Sawada T, Uchida M, Iijima H, Kimura K, Hirakawa K, et al. MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways. Int J Oncol. 2013;42(3):887–93.

    Article  CAS  Google Scholar 

  37. Kim SM, Kwon CH, Shin N, Park DY, Moon HJ, Kim GH, et al. Decreased Muc5AC expression is associated with poor prognosis in gastric cancer. Int J Cancer. 2014;134(1):114–24.

    Article  Google Scholar 

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Funding

This study was funded in part by the National Research Foundation (NRF), South Africa.

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Authors and Affiliations

  1. Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Liam Robinson, Marlene B. van Heerden, Keith D. Hunter & Willie F. P. van Heerden

  2. Department of Financial Management, Faculty of Economic and Management Sciences, University of Pretoria, Pretoria, South Africa

    Jason G. Ker-Fox

  3. Academic Unit of Oral and Maxillofacial Medicine and Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK

    Keith D. Hunter

Authors
  1. Liam Robinson
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  2. Marlene B. van Heerden
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  3. Jason G. Ker-Fox
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  4. Keith D. Hunter
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  5. Willie F. P. van Heerden
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Contributions

WvH, KH and LR all contributed to the study conception and design. The literature review was undertaken by LR with guidance from WvH. Material preparation, data collection and analysis were performed by WvH, KH and LR. Immunohistochemical stains and FISH analysis were performed by MvH. Statistical analysis was performed by JK-F. The first draft of the manuscript was written by LR, with all authors giving feedback and corrections. All authors read and approved the final manuscript.

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Correspondence to Willie F. P. van Heerden.

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The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the University of Pretoria, Faculty of Health Sciences Research Ethics Committee (Reference no.: 759/2019).

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Robinson, L., van Heerden, M.B., Ker-Fox, J.G. et al. Expression of Mucins in Salivary Gland Mucoepidermoid Carcinoma. Head and Neck Pathol 15, 491–502 (2021). https://doi.org/10.1007/s12105-020-01226-z

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  • DOI: https://doi.org/10.1007/s12105-020-01226-z

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