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TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer

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Abstract

The molecular alterations of pancreatic acinar cell carcinomas (ACCs) are poorly understood and have been reported as being different from those in ductal adenocarcinomas. Loss of TP53 gene function in the pathogenesis of ACCs is controversial since contradictory findings have been published. A comprehensive analysis of the different possible genetic and epigenetic mechanisms leading to TP53 alteration in ACC has never been reported and hence the role of TP53 in the pathogenesis and/or progression of ACC remains unclear. We investigated TP53 alterations in 54 tumor samples from 44 patients, including primary and metastatic ACC, using sequencing analysis, methylation-specific multiplex ligation probe amplification, fluorescence in situ hybridization, and immunohistochemistry. TP53 mutations were found in 13 % of primary ACCs and in 31 % of metastases. Primary ACCs and metastases showed the same mutational profile, with the exception of one case, characterized by a wild-type sequence in the primary carcinoma and a mutation in the corresponding metastasis. FISH analysis revealed deletion of the TP53 region in 53 % of primary ACCs and in 50 % of metastases. Promoter hypermethylation was found in one case. The molecular alterations correlated well with the immunohistochemical findings. A statistically significant association was found between the combination of mutation of one allele and loss of the other allele of TP53 and worse survival.

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Acknowledgments

The authors thank prof. Gianni Bussolati for providing his cases.

Author information

Authors and Affiliations

  1. Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy

    Stefano La Rosa & Maria Grazia Tibiletti

  2. Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy

    Barbara Bernasconi, Daniela Furlan, Nora Sahnane, Carlo Capella & Fausto Sessa

  3. Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland

    Milo Frattini & Francesca Molinari

  4. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Alessandro Vanoli

  5. Pathology Unit, San Raffaele Scientific Institute, Milan, Italy

    Luca Albarello

  6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Lizhi Zhang

  7. Department of Pathology, Kurashiki Central Hospital, Kurashiki, Japan

    Kenji Notohara

  8. Centre de Pathologie, Strasbourg, France

    Selenia Casnedi

  9. Department of Pathology, Hospital De Hautepierre, Strasbourg, France

    Marie-Pierre Chenard

  10. Department of Pathology, Emory University, Atlanta, GA, USA

    Volkan Adsay

  11. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

    Sofia Asioli

Authors
  1. Stefano La Rosa
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  2. Barbara Bernasconi
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  3. Milo Frattini
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  4. Maria Grazia Tibiletti
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  5. Francesca Molinari
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  6. Daniela Furlan
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  7. Nora Sahnane
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  8. Alessandro Vanoli
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  9. Luca Albarello
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  10. Lizhi Zhang
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  11. Kenji Notohara
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  12. Selenia Casnedi
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  13. Marie-Pierre Chenard
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  14. Volkan Adsay
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  15. Sofia Asioli
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  16. Carlo Capella
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  17. Fausto Sessa
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Corresponding author

Correspondence to Stefano La Rosa.

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La Rosa, S., Bernasconi, B., Frattini, M. et al. TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer. Virchows Arch 468, 289–296 (2016). https://doi.org/10.1007/s00428-015-1882-9

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  • DOI: https://doi.org/10.1007/s00428-015-1882-9

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