Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway

Susan C. Abraham, Tsung Teh Wu, Ralph H. Hruban, Jae Hyuk Lee, Charles J. Yeo, Kevin Conlon, Murray Brennan, John L. Cameron, David S. Klimstra

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/β-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/β-catenin pathway and for allelic loss on chromosome lip. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome lip was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/β-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the β-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.

Original languageEnglish (US)
Pages (from-to)953-962
Number of pages10
JournalAmerican Journal of Pathology
Volume160
Issue number3
StatePublished - 2002
Externally publishedYes

Fingerprint

Acinar Cell Carcinoma
Catenins
Loss of Heterozygosity
Chromosomes
Microsatellite Instability
Lip
Pancreatic Carcinoma
Mutation
Adenocarcinoma
Exocrine Pancreas
Pancreatic Neoplasms
Oncogenes
Microsatellite Repeats

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma : Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway. / Abraham, Susan C.; Wu, Tsung Teh; Hruban, Ralph H.; Lee, Jae Hyuk; Yeo, Charles J.; Conlon, Kevin; Brennan, Murray; Cameron, John L.; Klimstra, David S.

In: American Journal of Pathology, Vol. 160, No. 3, 2002, p. 953-962.

Research output: Contribution to journalArticle

Abraham, SC, Wu, TT, Hruban, RH, Lee, JH, Yeo, CJ, Conlon, K, Brennan, M, Cameron, JL & Klimstra, DS 2002, 'Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway', American Journal of Pathology, vol. 160, no. 3, pp. 953-962.
Abraham, Susan C. ; Wu, Tsung Teh ; Hruban, Ralph H. ; Lee, Jae Hyuk ; Yeo, Charles J. ; Conlon, Kevin ; Brennan, Murray ; Cameron, John L. ; Klimstra, David S. / Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma : Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway. In: American Journal of Pathology. 2002 ; Vol. 160, No. 3. pp. 953-962.
@article{09bc1d818b64450a859b2b0a8d1c23f1,
title = "Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway",
abstract = "Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/β-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/β-catenin pathway and for allelic loss on chromosome lip. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome lip was the most common genetic alteration in ACCs, present in 50{\%} (6 of 12 informative cases). Molecular alterations in the APC/β-catenin pathway were detected in 23.5{\%} (4 of 17) of the carcinomas, including one ACC with an activating mutation of the β-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6{\%}) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4{\%}) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.",
author = "Abraham, {Susan C.} and Wu, {Tsung Teh} and Hruban, {Ralph H.} and Lee, {Jae Hyuk} and Yeo, {Charles J.} and Kevin Conlon and Murray Brennan and Cameron, {John L.} and Klimstra, {David S.}",
year = "2002",
language = "English (US)",
volume = "160",
pages = "953--962",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma

T2 - Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway

AU - Abraham, Susan C.

AU - Wu, Tsung Teh

AU - Hruban, Ralph H.

AU - Lee, Jae Hyuk

AU - Yeo, Charles J.

AU - Conlon, Kevin

AU - Brennan, Murray

AU - Cameron, John L.

AU - Klimstra, David S.

PY - 2002

Y1 - 2002

N2 - Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/β-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/β-catenin pathway and for allelic loss on chromosome lip. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome lip was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/β-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the β-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.

AB - Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/β-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/β-catenin pathway and for allelic loss on chromosome lip. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome lip was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/β-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the β-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.

UR - http://www.scopus.com/inward/record.url?scp=0036120621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036120621&partnerID=8YFLogxK

M3 - Article

C2 - 11891193

AN - SCOPUS:0036120621

VL - 160

SP - 953

EP - 962

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -