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

• Published in: Virchows Archiv : an international journal of pathology Vol. 473; no. 4; pp. 435 - 441
• Main Authors: La Rosa, Stefano, Bernasconi, Barbara, Vanoli, Alessandro, Sciarra, Amedeo, Notohara, Kenji, Albarello, Luca, Casnedi, Selenia, Billo, Paola, Zhang, Lizhi, Tibiletti, Maria Grazia, Sessa, Fausto
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2018; Springer Nature B.V
• Subjects: Amplification; c-Myc protein; Cancer; Chromosome 8; Chromosomes; Cloning; Fluorescence; Fluorescence in situ hybridization; Gene amplification; Hybridization analysis; Immunoreactivity; Medical prognosis; Medicine; Medicine & Public Health; Molecular chains; Myc protein; Neuroendocrine tumors; Original Article; Pancreas; Pancreatic carcinoma; Pathogenesis; Pathology; Prognosis; Protein expression; Proteins; Amplification; Acinar cell carcinoma; MANEC; Prognosis; c-myc; MiNEN; Pancreas
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-018-2366-5

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.