c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers

Stefano La Rosa, Barbara Bernasconi, Alessandro Vanoli, Amedeo Sciarra, Kenji Notohara, Luca Albarello, Selenia Casnedi, Paola Billo, Lizhi Zhang, Maria Grazia Tibiletti, Fausto Sessa

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7 Scopus citations

Abstract

The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs.

Original languageEnglish (US)
Pages (from-to)435-441
Number of pages7
JournalVirchows Archiv
Volume473
Issue number4
DOIs
StatePublished - Oct 1 2018

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Keywords

  • Acinar cell carcinoma
  • Amplification
  • MANEC
  • MiNEN
  • Pancreas
  • Prognosis
  • c-myc

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

La Rosa, S., Bernasconi, B., Vanoli, A., Sciarra, A., Notohara, K., Albarello, L., Casnedi, S., Billo, P., Zhang, L., Tibiletti, M. G., & Sessa, F. (2018). c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers. Virchows Archiv, 473(4), 435-441. https://doi.org/10.1007/s00428-018-2366-5