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Virchows Archiv

, Volume 458, Issue 5, pp 583–592 | Cite as

Aberrant PLAG1 expression in pleomorphic adenomas of the salivary gland: a molecular genetic and immunohistochemical study

  • Atsuji MatsuyamaEmail author
  • Masanori Hisaoka
  • Yuichi Nagao
  • Hiroshi Hashimoto
Original Article

Abstract

The morphologic distinction of pleomorphic adenoma from other benign or low-grade salivary gland tumors is sometimes difficult and problematic because of their potentially overlapping histological patterns. A subset of pleomorphic adenoma harbors specific gene alterations involving PLAG1 or HMGA2, and the detection of these fusion genes and their products using formalin-fixed, paraffin-embedded (FFPE) tumor specimens may be a useful diagnostic adjunct. In the present study, gene fusions involving PLAG1 or HMGA2 were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis, with FFPE tumor tissues and immunohistochemical expression of PLAG1 in 45 pleomorphic adenomas, using a commercially available antibody. RT-PCR analyses identified the CTNNB1-PLAG1, LIFR-PLAG1, CHCHD7-PLAG1, and HMGA2-WIF1 fusion transcripts in eight, two, one, and one case, respectively. The TCEA1-PLAG1, HMGA2-FHIT, and HMGA2-NFIB fusion transcripts were not detected. Immunohistochemically, tumor cells in all 45 pleomorphic adenomas were positive for PLAG1, irrespective of PLAG1 rearrangements, even in the case with the HMGA2-WIF1 fusion transcript. Tumor cells displaying myoepithelial or cartilaginous differentiation were almost constantly positive for PLAG1, whereas a limited expression was observed in glandular or keratinizing cells. Among the 46 tumors other than pleomorphic adenoma, 4 carcinomatous components of carcinomas ex pleomorphic adenoma were positive for PLAG1, the other 39 were negative for PLAG1, and the remaining 3 were only faintly and/or focally stained, indicating that the immunohistochemical detection of PLAG1 is diagnostically useful. The present results also suggest that overexpression of PLAG1 is essential for the tumorigenesis of pleomorphic adenomas, although the mechanisms mediating PLAG1 overexpression seem to be variable.

Keywords

Pleomorphic adenoma PLAG1 HMGA2 Immunohistochemistry RT-PCR 

Notes

Acknowledgments

The authors thank Kazumi Tanaka for her technical assistance.

Conflict of interest

We declare that we have no conflict of interest.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Atsuji Matsuyama
    • 1
    Email author
  • Masanori Hisaoka
    • 1
  • Yuichi Nagao
    • 1
  • Hiroshi Hashimoto
    • 1
  1. 1.Department of Pathology and Oncology, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan

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