Skip to main content

Advertisement

SpringerLink
Log in

Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Skalova A, Jakel K (2005) Myoepithelial carcinoma. In: Barnes L, Eveson J, Reichart P, Sidransky D (eds) World health organization classification of head and neck tumours. IARC, Lyon, pp 240–241

    Google Scholar 

  2. Savera AT, Sloman A, Huvos AG, Klimstra DS (2000) Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol 24:761–774

    Article  CAS  PubMed  Google Scholar 

  3. Kane SV, Bagwan IN (2010) Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 51 cases in a tertiary cancer center. Arch Otolaryngol Head Neck Surg 136:702–712. doi:10.1001/archoto.2010.104

    Article  PubMed  Google Scholar 

  4. Kong M, Drill EN, Morris L, West L, Klimstra D, Gonen M, Ghossein R, Katabi N (2015) Prognostic factors in myoepithelial carcinoma of salivary glands: a clinicopathologic study of 48 cases. Am J Surg Pathol 39(7):931–938. doi:10.1097/PAS.0000000000000452, PubMed

    Article  PubMed  Google Scholar 

  5. Skálová A, Weinreb I, Hyrcza M, Simpson RH, Laco J, Agaimy A, Vazmitel M, Majewska H, Vanecek T, Talarčik P, Manajlovic S, Losito SN, Šteiner P, Klimkova A, Michal M (2015) Clear cell myoepithelial carcinoma of salivary glands showing EWSR1 rearrangement: molecular analysis of 94 salivary gland carcinomas with prominent clear cell component. Am J Surg Pathol 39(3):338–348. doi:10.1097/PAS.0000000000000364, PubMed

    Article  PubMed  Google Scholar 

  6. Weinberg R (2007) pRB and control of the cell cycle clock. In: Weinberg R (ed) The biology of cancer, firstth edn. Garland Science, New York, pp 255–306

    Google Scholar 

  7. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9:153–166. doi:10.1038/nrc2602

    Article  CAS  PubMed  Google Scholar 

  8. Dominguez Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, Gu W, Gautier J, Dalla Favera R (2007) Nontranscriptional control of DNA replication by c-Myc. Nature 448:445–451. doi:10.1038/nature05953

    Article  CAS  PubMed  Google Scholar 

  9. Van Riggelen J, Yetil A, Felsher DW (2010) MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10:301–309. doi:10.1038/nrc2819

    Article  PubMed  Google Scholar 

  10. Eilers M, Eisenman RN (2008) Myc’s broad reach. Genes Dev 22:2755–2766. doi:10.1101/gad.1712408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nagao T, Sugano I, Ishida Y, Tajima Y, Matsuzaki O, Konno A, Kondo Y, Nagao K (1998) Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases. Cancer 83:1292–1299

    Article  CAS  PubMed  Google Scholar 

  12. Di Palma S, Guzzo M (1993) Malignant myoepithelioma of salivary glands: clinicopathological features of ten cases. Virchows Arch A Pathol Anat Histopathol 423:389–396

    Article  PubMed  Google Scholar 

  13. Cai C, Dehner LP, El-Mofty SK (2013) In myofibroblastic sarcomas of the head and neck, mitotic activity and necrosis define grade: a case study and literature review. Virchows Arch 463(6):827–836. doi:10.1007/s00428-013-1494-1, Epub 2013 Oct 17. Review. PubMed

    Article  PubMed  Google Scholar 

  14. Pichler M, Hutterer GC, Chromecki TF, Pummer K, Mannweiler S, Zigeuner R (2013) Presence and extent of histological tumour necrosis is an adverse prognostic factor in papillary type 1 but not in papillary type 2 renal cell carcinoma. Histopathology 62:219–228

    Article  PubMed  Google Scholar 

  15. Lohse CM, Cheville JC (2005) A review of prognostic pathologic features and algorithms for patients treated surgically for renal cell carcinoma. Clin Lab Med 25:433–464

    Article  PubMed  Google Scholar 

  16. Yanai H, Mani Y, Notohara K, Takada S, Yoshino T (2010) Uterine leiomyosarcoma arising in leiomyoma: Clinicopathological study of four cases and literature review. Pathol Int 60:506–509

    Article  PubMed  Google Scholar 

  17. Katabi N, Gomez D, Klimstra DS, Carlson DL, Lee N, Ghossein R (2010) Prognostic factors of recurrence in salivary carcinoma ex pleomorphic adenoma, with emphasis on the carcinoma histologic subtype: a clinicopathologic study of 43 cases. Hum Pathol 41:927–934. doi:10.1016/j.humpath.2009.12.011

    Article  PubMed  Google Scholar 

  18. Klein JD, Grandis JR (2010) The molecular pathogenesis of head and neck cancer. Cancer Biol Ther 9:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Calcagno DQ, Leal MF, Assumpcao PP, Smith MA, Burbano RR (2008) MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol 14:5962–5968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vékony H, Röser K, Löning T, Ylstra B, Meijer GA, Van Wieringen WN et al (2009) Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas. Genes Chromosomes Cancer 48:202–212

    Article  PubMed  Google Scholar 

  21. Etges A, Nunes FD, Ribeiro KC, Araujo VC (2004) Immunohistochemical expression of retinoblastoma pathway proteins in normal salivary glands and in salivary gland tumours. Oral Oncol 40:326–331

    Article  CAS  PubMed  Google Scholar 

  22. Vekony H, Roser K, Loning T, Raaphorst FM, Leemans CR, Van Der Waal I, Bloemena E (2008) Deregulated expression of p16INK4a and p53 pathway members in benign and malignant myoepithelial tumours of the salivary glands. Histopathology 53:658–666. doi:10.1111/j.1365-2559.2008.03184.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge financial support from the Finnish Cancer Society, Finska Läkaresällskapet and the Maritza and Reino Salonen Foundation. The technical assistance of Ms. Eija Heiliö and Ms. Tuija Järvinen is kindly acknowledged.

Author information

Authors and Affiliations

  1. Department of Pathology, Haartman Institute, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, FIN-00014, Helsinki, Finland

    F. Passador-Santos, M. Grönroos & I. Leivo

  2. Department of Pathology, São Leopoldo Mandic Research Centre, Campinas, Brazil

    F. Passador-Santos

  3. Department of Otolaryngology and Surgical Oncology, University of Toronto, Toronto, ON, M5S, Canada

    J. Irish, R. Gilbert & P. Gullane

  4. Department of Pathology, University of Toronto, Toronto, ON, M5S, Canada

    B. Perez-Ordonez

  5. Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 220, FI-00029 HUS, Helsinki, Finland

    A. Mäkitie

  6. Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, SE-171 77, Stockholm, Sweden

    A. Mäkitie

  7. Department of Pathology, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland

    I. Leivo

Authors
  1. F. Passador-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Grönroos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Irish
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Gullane
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Perez-Ordonez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Mäkitie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. Leivo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Passador-Santos.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Passador-Santos, F., Grönroos, M., Irish, J. et al. Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands. Virchows Arch 468, 305–312 (2016). https://doi.org/10.1007/s00428-015-1889-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-015-1889-2

Keywords

Search

Navigation