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, B Bernasconi, A Vanoli, Amedeo Sciarra, K Notohara, L Albarello, S Casnedi, P Billo, L Zhang, MG Tibiletti, Fausto Sessa

Research output: Contribution to journalArticle

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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
Original languageEnglish
Pages (from-to)435-441
Number of pages7
JournalVirchows Archiv
Volume473
Issue number4
DOIs
Publication statusPublished - 2018

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Acinar Cell Carcinoma
Proto-Oncogene Proteins c-myc
Chromosomes, Human, Pair 8
Neuroendocrine Carcinoma
Neoplasms
Gene Amplification
Clone Cells
Pancreatic Carcinoma
Centromere
Nuclear Proteins
Diploidy
Fluorescence In Situ Hybridization
Germany

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c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers. / La Rosa, Stefano; Bernasconi, B; Vanoli, A; Sciarra, Amedeo; Notohara, K; Albarello, L; Casnedi, S; Billo, P; Zhang, L; Tibiletti, MG; Sessa, Fausto.

In: Virchows Archiv, Vol. 473, No. 4, 2018, p. 435-441.

Research output: Contribution to journalArticle

La Rosa, S, Bernasconi, B, Vanoli, A, Sciarra, A, Notohara, K, Albarello, L, Casnedi, S, Billo, P, Zhang, L, Tibiletti, MG & 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, vol. 473, no. 4, pp. 435-441. https://doi.org/10.1007/s00428-018-2366-5
La Rosa, Stefano ; Bernasconi, B ; Vanoli, A ; Sciarra, Amedeo ; Notohara, K ; Albarello, L ; Casnedi, S ; Billo, P ; Zhang, L ; Tibiletti, MG ; Sessa, Fausto. / c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers. In: Virchows Archiv. 2018 ; Vol. 473, No. 4. pp. 435-441.
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AU - Notohara, K

AU - Albarello, L

AU - Casnedi, S

AU - Billo, P

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AU - Sessa, Fausto

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N2 - 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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

AB - 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. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

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