Skip to main content

Advertisement

SpringerLink
Log in

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

  • Original Paper
  • Published:
Cellular Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 20 August 2011

Abstract

Background

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features, and to compare results to solid ACC.

Methods

Genome wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, four with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), and five solid ACC. In addition, Ki67 index and p53 immunopositivity was assessed.

Results

ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.

Conclusion

ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. A.K. El-Naggar, A.G. Huvos, Adenoid cystic carcinoma, in World Organization Classification of Tumors. Pathology & Genetics Head and Neck Tumours, ed. by L. Barnes, J.W. Everson, P. Reichart et al. (IARC Press, Lyon, 2005), pp. 221–222

    Google Scholar 

  2. K.H. Perzin, P. Gullane, A.C. Clairmont, Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer 42, 265–282 (1978)

    Article  PubMed  CAS  Google Scholar 

  3. P.A. Szanto, M.A. Luna, M.E. Tortoledo et al., Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 54, 1062–1069 (1984)

    Article  PubMed  CAS  Google Scholar 

  4. D.E. da Cruz Perez, F. de Abreu Alves, I. Nobuko Nishimoto et al., Prognostic factors in head and neck adenoid cystic carcinoma. Oral Oncol 42, 139–146 (2005)

    Article  PubMed  Google Scholar 

  5. G. Franzén, S. Nordgård, M. Boysen et al., DNA content in adenoid cystic carcinomas. Head Neck 17, 49–55 (1995)

    Article  PubMed  Google Scholar 

  6. H. Papadaki, S.D. Finkelstein, S. Kounelis et al., The role of p53 mutation and protein expression in primary and recurrent adenoid cystic carcinoma. Hum Pathol 27, 567–572 (1996)

    Article  PubMed  CAS  Google Scholar 

  7. T. Nagao, T.A. Gaffey, H. Serizawa et al., Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases. Mod Pathol 16, 1265–1272 (2003)

    Article  PubMed  Google Scholar 

  8. F. Ide, K. Mishima, I. Saito, Small foci of high-grade carcinoma cells in adenoid cystic carcinoma represent an incipient phase of dedifferentiation. Histopathology 43, 604–606 (2003)

    Article  PubMed  CAS  Google Scholar 

  9. Y. Chau, T. Hongyo, K. Aozasa et al., Dedifferentiation of adenoid cystic carcinoma: report of a case implicating p53 gene mutation. Hum Pathol 32, 1403–1407 (2001)

    Article  PubMed  CAS  Google Scholar 

  10. M.A. Moles, I.R. Avila, A.R. Archilla, Dedifferentiation occurring in adenoid cystic carcinoma of the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88, 177–180 (1999)

    Article  PubMed  CAS  Google Scholar 

  11. W. Cheuk, J.K. Chan, R.K. Ngan, Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon complication associated with an accelerated clinical course. Am J Surg Pathol 23, 465–472 (1999)

    Article  PubMed  CAS  Google Scholar 

  12. K. Sato, Y. Ueda, A. Sakurai et al., Adenoid cystic carcinoma of the maxillary sinus with gradual histologic transformation to high-grade adenocarcinoma: a comparative report with dedifferentiated carcinoma. Virchows Arch 448, 204–208 (2006)

    Article  PubMed  Google Scholar 

  13. R.R. Seethala, J.L. Hunt, Z.W. Baloch et al., Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature. Am J Surg Pathol 31, 1683–1694 (2007)

    Article  PubMed  Google Scholar 

  14. A. Handra-Luca, D. Planchard, P. Fouret, Docetaxel-cisplatin-radiotherapy in adenoid cystic carcinoma with high-grade transformation. Oral Oncol 45, 208–209 (2009)

    Article  Google Scholar 

  15. K.P. Malhotra, V. Agrawal, R. Pandey, High grade transformation in adenoid cystic carcinoma of the parotid: report of a case with cytologic, histologic and immunohistochemical study. Head Neck Pathol 3, 310–314 (2009)

    Article  PubMed  Google Scholar 

  16. V.L. Bonfitto, A.P. Demasi, A.F. Costa et al., High-grade transformation of adenoid cystic carcinomas may result in adenocarcinomas with wide spectrum of differentiation. A study of the expression of GLUT1 glucose transporter and of mitochondrial antigen in the transformed component. J Clin Pathol 63, 615–619 (2010)

    Article  PubMed  CAS  Google Scholar 

  17. H. Vékony, B. Ylstra, S.M. Wilting et al., DNA copy number gains at loci of growth factors and their receptors in salivary gland adenoid cystic carcinoma. Clin Cancer Res 13, 3133–3139 (2007)

    Article  PubMed  Google Scholar 

  18. B.M. Wening, Neoplasmas of the salivary glands, in Atlas of head and neck pathology, ed. by B.M. Wening, C.S. Heffess (China, Saunders Elsevier, 2008), pp. 628–631

    Google Scholar 

  19. T.E. Buffart, D. Israeli, M. Tijssen et al., Across array comparative genomic hybridization: a strategy to reduce reference channel hybridizations. Genes Chromosom Cancer 47, 994–1004 (2008)

    Article  PubMed  CAS  Google Scholar 

  20. G. Stenman, J. Sandros, R. Dahlenfors et al., 6q- and loss of the Y chromosome–two common deviations in malignant human salivary gland tumors. Cancer Genet Cytogenet 22, 283–293 (1986)

    Article  PubMed  CAS  Google Scholar 

  21. K. Higashi, Y. Jin, M. Johansson et al., Rearrangement of 9p13 as the primary chromosomal aberration in adenoid cystic carcinoma of the respiratory tract. Genes Chromosom Cancer 3, 21–23 (1991)

    Article  PubMed  CAS  Google Scholar 

  22. A. Nordkvist, J. Mark, H. Gustafsson et al., Non-random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands. Genes Chromosom Cancer 10, 115–121 (1994)

    Article  PubMed  CAS  Google Scholar 

  23. L. Queimado, A. Reis, I. Fonseca et al., A refined localization of two deleted regions in chromosome 6q associated with salivary gland carcinomas. Oncogene 16, 83–88 (1998)

    Article  PubMed  CAS  Google Scholar 

  24. M. Kishi, M. Nakamura, M. Nishimine et al., Loss of heterozygosity on chromosome 6q correlates with decreased thrombospondin-2 expression in human salivary gland carcinomas. Cancer Sci 94, 530–535 (2003)

    Article  PubMed  CAS  Google Scholar 

  25. W. El-Rifai, S. Rutherford, S. Knuutila et al., Novel DNA copy number losses in chromosome 12q12–q13 in adenoid cystic carcinoma. Neoplasia 3, 173–178 (2001)

    Article  PubMed  CAS  Google Scholar 

  26. R.H. Rao, D. Roberts, Y.J. Zhao 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 14, 5181–5187 (2008)

    Article  PubMed  CAS  Google Scholar 

  27. I. Stallmach, P. Zenklusen, P. Komminoth et al., Loss of heterozygosity at chromosome 6q23-25 correlates with clinical and histologic parameters in salivary gland adenoid cystic carcinoma. Virchows Arch 440, 77–84 (2002)

    Article  PubMed  CAS  Google Scholar 

  28. S. Rutherford, Y. Yu, C.A. Rumpel et al., Chromosome 6 deletion and candidate tumor suppressor genes in adenoid cystic carcinoma. Cancer Lett 236, 309–317 (2006)

    Article  PubMed  CAS  Google Scholar 

  29. J.M. Geurts, E.F. Schoenmakers, E. Röijer et al., Identification of NFIB as recurrent translocation partner gene of HMGIC in pleomorphic adenomas. Oncogene 16, 865–872 (1998)

    Article  PubMed  CAS  Google Scholar 

  30. M. Persson, Y. Andrén, J. Mark et al., Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA 106, 18740–18744 (2009)

    Article  PubMed  CAS  Google Scholar 

  31. E. Kennah, A. Ringrose, L.L. Zhou et al., Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells. Blood 113, 4646–4655 (2009)

    Article  PubMed  CAS  Google Scholar 

  32. L.L. Zhou, Y. Zhao, A. Ringrose et al., AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells. J Exp Med 205, 2657–2671 (2008)

    Article  PubMed  CAS  Google Scholar 

  33. T. Soussi, The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann NY Acad Sci 910, 121–137 (2000)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by project EMER 07–048 and PI08-153 of Fondos de Investigación Sanitaria (FIS), and RD06/0020/0034 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spain. Supported in Brazil by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant number 09/54377-2 and 10/51571-0; Programa de Mobilidade Internacional do Banco Santander/Universidade Estadual de Campinas (UNICAMP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant number 473641/2008-9. Special thanks to Bauke Ylstra of Microarray Laboratory of VU University Medical Center, Amsterdam, The Netherlands.

Author information

Authors and Affiliations

  1. Department of Pathology, University of Campinas/UNICAMP, Campinas, Brazil

    Ana Flávia Costa & Albina Altemani

  2. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    Hedy Vékony & Elisabeth Bloemena

  3. Department of Pathology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, Spain

    Florentino Fresno

  4. Department of Otolaryngology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, Spain

    Carlos Suárez, José Luis Llorente & Mario Hermsen

  5. Departamento de Anatomia Patológica, Faculdade de Ciências Médicas, UNICAMP, Rua Tessália Vieira de Camargo 126, ZIP Code 13084-971, Campinas, São Paulo, Brazil

    Ana Flávia Costa

Authors
  1. Ana Flávia Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Albina Altemani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hedy Vékony
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elisabeth Bloemena
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Florentino Fresno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlos Suárez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José Luis Llorente
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mario Hermsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Flávia Costa.

Additional information

This paper is a reprint from ‘Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type, Ana Flávia Costa, Albina Altemani, Hedy Vékony, Elisabeth Bloemena, Florentino Fresno, Carlos Suárez, José Luis Llorente, Mario Hermsen’ originally published in Analytical Cellular Pathology/Cellular Oncology, Volume 33, number 5–6, 2010, pp. 217–228, IOS Press.

An erratum to this article can be found at http://dx.doi.org/10.1007/s13402-011-0057-1

Rights and permissions

Reprints and permissions

About this article

Cite this article

Costa, A.F., Altemani, A., Vékony, H. et al. Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type. Cell Oncol. 34, 369–379 (2011). https://doi.org/10.1007/s13402-011-0037-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-011-0037-5

Keywords

Search

Navigation