Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma
Open accessAbstract
Little or no data exist concerning the inactivation of tumor suppressor genes in intraductal lesions surrounding invasive ductal pancreatic carcinomas. Using a novel improved primer extension and preamplification polymerase chain reaction, we analyzed microdissected paraffin-embedded specimens of pancreatic carcinoma (n = 29) and their corresponding pancreatic intraductal lesions (PIL, n = 331) for loss of heterozygosity (LOH) of p16(INK4), DPC4, and p53 by microsatellite analysis and for p53 protein by immunohistochemistry. LOH at the p16(INK4) locus (9p21) was found in nine of 22 informative tumors (41%), in 15 of 25 tumors (60%) at the DPC4 locus (18q21.1), and in 22 of 27 tumors (81%) at the p53 locus (17p13). Homozygous deletions of p16(INK4) and DPC4 were found in eight of 22 (36%) and four of 25 tumors (16%), respectively. Furthermore, 24 of 29 tumors (83%) revealed considerable intratumoral genetic heterogeneity. In 165 of 277 PILs (60%) having suitable DNA for microsatellite analysis, alterations in at least one tumor suppressor gene were found. In individual PILs, up to three alterations were detected, and p53 LOH occurred even in morphologically normal-appearing ductal epithelium near the tumor. Although deletions of all three tumor suppressor genes were found in PILs without nuclear atypia, there was a tendency toward earlier LOH of p16(INK4) compared to DPC4 and p53 in these lesions. LOH in tumors accompanied positive p53 immunohistochemistry in 81% but only in 38% in PILs.
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About 40% of pancreatic ductal adenocarcinomas have both mutated TP53 and deleted ARF.
“For example, approximately 40% of pancreatic ductal adenocarcinomas have mutated TP53 and deleted ARF (Heinmoller, et al., 2000; Hustinx, et al., 2005; Maitra, et al., 2003).”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Heinmoller, et al., 2000
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ResultThe Mdm network and its regulation of p53 activities: a rheostat of cancer risk
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- Authors
- Heinmöller, E., Dietmaier, W., Zirngibl, H., Heinmöller, P., Scaringe, W., Jauch, K.-W., Hofstädter, F., & Rüschoff, J.
- Affiliations
- City Of Hope National Medical Center (US)
- University Hospital Regensburg (DE)
- Witten/Herdecke University (DE)
- Klinikum Kassel (DE)
- Corresponding author
- Heinmöller, Petra
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 157
- Issue
- 1
- Pages
- 83-92
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1850206
- OpenAlex
- W2059330620
- Cited by
- 121
- References
- 60
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 6 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 1 · 2012: 3
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- pancreatic cancer, intraductal lesions, precancerous lesions, tumor suppressor, loss of heterozygosity, p16INK4, SMAD4, p53, microsatellite analysis, intratumoral genetic heterogeneity, p53 expression, 9p21, 17p13, microdissection, paraffin-embedded tissue
- MeSH terms
- Carcinoma, Intraductal, Noninfiltrating, DNA-Binding Proteins, Humans, Immunohistochemistry, Neoplasm Staging, Pancreas, Pancreatic Neoplasms, Precancerous Conditions, Trans-Activators, Tumor Suppressor Protein p53, Microsatellite Repeats, Loss of Heterozygosity, Cyclin-Dependent Kinase Inhibitor p16, Smad4 Protein
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