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

Stefano La Rosa, Barbara Bernasconi, Milo Frattini, Maria Grazia Tibiletti, Francesca Molinari, Daniela Furlan, Nora Sahnane, Alessandro Vanoli, Luca Albarello, Lizhi Zhang, Kenji Notohara, Selenia Casnedi, Marie Pierre Chenard, Volkan Adsay, Sofia Asioli, C. Capella, F. Sessa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)289-296
Number of pages8
JournalVirchows Archiv - A Pathological Anatomy and Histopathology
Volume468
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Acinar cell carcinoma
  • p53
  • Pancreas
  • TP53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)
  • Molecular Biology
  • Cell Biology

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  • Cite this

    La Rosa, S., Bernasconi, B., Frattini, M., Tibiletti, M. G., Molinari, F., Furlan, D., Sahnane, N., Vanoli, A., Albarello, L., Zhang, L., Notohara, K., Casnedi, S., Chenard, M. P., Adsay, V., Asioli, S., Capella, C., & Sessa, F. (2016). TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer. Virchows Archiv - A Pathological Anatomy and Histopathology, 468(3), 289-296. https://doi.org/10.1007/s00428-015-1882-9