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Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles

Modern Pathologyvolume 31pages12111225 (2018) | Download Citation

Abstract

Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

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Acknowledgements

We thank Sanni Pedersen, Heidi Ugleholdt, and Pernille Frederiksen for brilliant technical assistance. The study was funded by Einar Willumsen Foundation, Merchant Kristjan Kjær and wife Margrethe Kjær’s Foundation, The Danielsen Foundation, Resino A/S, Else and Mogens Wedell-Wedellsborg’s Foundation, Region Zealand’s Research Fund, Hans Skouby and wife Emma Skouby’s Foundation, and the A.P. Møller Foundation for the Advancement of Medical Research.

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Affiliations

  1. Department of Otorhinolaryngology and Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark

    • Simon Andreasen
    •  & Preben Homøe
  2. Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark

    • Simon Andreasen
    •  & Irene Wessel
  3. Department of Clinical Research, Unit of Human Genetics, University of Southern Denmark, Odense, Denmark

    • Qihua Tan
  4. Department of Pathology, Rigshospitalet, Copenhagen, Denmark

    • Tina Klitmøller Agander
    •  & Steffen Heegaard
  5. Department of Pathology, Faculty of Medicine, Charles University in Prague, Pilsen, Czech Republic

    • Petr Steiner
  6. Bioptic Laboratory Ltd, Molecular Pathology Laboratory, Pilsen, Czech Republic

    • Petr Steiner
  7. Department of ORL–Head and Neck Surgery, Odense University Hospital, Odense, Denmark

    • Kristine Bjørndal
  8. Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

    • Estrid Høgdall
  9. Department of Pathology, Odense University Hospital, Odense, Denmark

    • Stine Rosenkilde Larsen
  10. Department of Pathology, Aalborg University Hospital, Aalborg, Denmark

    • Daiva Erentaite
  11. Department of Pathology, Zealand University Hospital, Roskilde, Denmark

    • Caroline Holkmann Olsen
  12. Department of Pathology, Aarhus University Hospital, Aarhus, Denmark

    • Benedicte Parm Ulhøi
  13. Department of Ophthalmology, Rigshospitalet-Glostrup, Copenhagen, Denmark

    • Sarah Linéa von Holstein
    •  & Steffen Heegaard
  14. Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark

    • Sarah Linéa von Holstein

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Correspondence to Simon Andreasen.

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https://doi.org/10.1038/s41379-018-0005-y

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