Background: The role of p53 in the pathogenesis of pancreatic acinar cell carcinomas (ACCs) is not clear. A few studies, mainly using immunohistochemistry, suggested that p53 is not altered in ACCs, but the small number of cases considered and the molecular analyses performed did not provide defi nitive data. Moreover, p53 mutation in 1/5 ACCs (Mod Pathol 24:1229,2011) and a signifi cant (>50% of cells) p53 nuclear immunoreactivity (IR) in 27% of ACCs (Am J Surg Pathol 36:1782,2012) have been recently demonstrated. For these reasons, the role of p53 in the pathogenesis of ACCs still needs further investigation. Design: We investigate p53 alterations (mutation, methylation, and loss) in 44 ACCs using direct sequencing of exons 4-8, MS-MLPA, and FISH. In addition, we evaluated nuclear p53-IR by immunohistochemistry. Results: p53 mutations were found in 8/44 (18%) cases. They correlated with higher tumor stage (5 cases were at stage IV) and, in one case, it was observed in the metastasis of a primary p53 wild type ACC. p53 gene loss, including 17p13 deletion and monosomy of chromosome 17, was found in 50% of ACCs and it was associated with mutation in 4 cases. p53 methylation was observed in only one case. p53 alterations correlated with p53-IR. The simultaneous presence of both p53 mutation and loss correlated with worse prognosis (p:0.001). Conclusions: p53 alterations including mutations and cytogenetic loss are frequent in ACCs and correlated with higher tumor stage and a more aggressive behavior suggesting that p53 is not early involved in ACC tumorigenesis, but later in cancer progression.

P53 Alterations in Acinar Cell Carcinomas of the Pancreas: New Insights into the Pathogenesis of Such Rare Cancers

ASIOLI, SOFIA;
2014

Abstract

Background: The role of p53 in the pathogenesis of pancreatic acinar cell carcinomas (ACCs) is not clear. A few studies, mainly using immunohistochemistry, suggested that p53 is not altered in ACCs, but the small number of cases considered and the molecular analyses performed did not provide defi nitive data. Moreover, p53 mutation in 1/5 ACCs (Mod Pathol 24:1229,2011) and a signifi cant (>50% of cells) p53 nuclear immunoreactivity (IR) in 27% of ACCs (Am J Surg Pathol 36:1782,2012) have been recently demonstrated. For these reasons, the role of p53 in the pathogenesis of ACCs still needs further investigation. Design: We investigate p53 alterations (mutation, methylation, and loss) in 44 ACCs using direct sequencing of exons 4-8, MS-MLPA, and FISH. In addition, we evaluated nuclear p53-IR by immunohistochemistry. Results: p53 mutations were found in 8/44 (18%) cases. They correlated with higher tumor stage (5 cases were at stage IV) and, in one case, it was observed in the metastasis of a primary p53 wild type ACC. p53 gene loss, including 17p13 deletion and monosomy of chromosome 17, was found in 50% of ACCs and it was associated with mutation in 4 cases. p53 methylation was observed in only one case. p53 alterations correlated with p53-IR. The simultaneous presence of both p53 mutation and loss correlated with worse prognosis (p:0.001). Conclusions: p53 alterations including mutations and cytogenetic loss are frequent in ACCs and correlated with higher tumor stage and a more aggressive behavior suggesting that p53 is not early involved in ACC tumorigenesis, but later in cancer progression.
2014
MODERN PATHOLOGY
451A
451A
S La Rosa; B Bernasconi; M Frattini; N Sahnane; F Molinari; MG Tibiletti; D Furlan; L Zang; A Vanoli; S Casnedi; V Adsay; K Notohara; L Albarello; S Asioli; F Sessa; C Capella.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/388870
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