Identification and Analysis of Precursors to Invasive Pancreatic Cancer

Department of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Methods in molecular biology (Clifton, N.J.) (Impact Factor: 1.29). 01/2013; 980:1-12. DOI: 10.1007/978-1-62703-287-2_1
Source: PubMed


Precursor lesions of pancreatic cancer have been recognized about a century ago. The development of a consistent reproducible nomenclature and classification system for these lesions has been a major advance in the study of these noninvasive precursors. Pancreatic intraepithelial neoplasia (PanIN) as microscopic precursor lesions can be distinguished from mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMN) that are cystic and can often be recognized on imaging. Since precursor lesions harbor the unique chance to treat a patient before a fatal pancreatic cancer can arise a molecular characterization is essential to understand the biology and to find diagnostic and therapeutic targets to fight this disease of near uniform lethality. In order to study precursor lesions on a molecular level a meticulous isolation of the neoplastic cells is inevitable. We present the salient histopathologic and molecular features of precursor lesions of pancreatic cancer as well as methods that have proved to be useful within experimental studies.

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    • "Pancreatic intraepithelial neoplasia (PanIN) is the main precancerous lesion of PDAC, which further develops into early PDAC. These lesions are divided into low-grade PanIN (PanIN-I) and high-grade PanIN (PanIN-II and PanIN–III), according to the progression of pathomorphological changes [6], [7]. "
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    ABSTRACT: The monitoring of pancreatic ductal adenocarcinoma (PDAC) in high-risk populations is essential. Cathepsin E (CTSE) is specifically and highly expressed in PDAC and pancreatic intraepithelial neoplasias (PanINs), and its expression gradually increases along with disease progression. In this study, we first established an in situ 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced rat model for PanINs and PDAC and then confirmed that tumorigenesis properties in this model were consistent with those of human PDAC in that CTSE expression gradually increased with tumor development using histology and immunohistochemistry. Then, using in vivo imaging of heterotopically implanted tumors generated from CTSE- overexpressing cells (PANC-1-CTSE) in nude mice and in vitro imaging of PanINs and PDAC in DMBA-induced rats, the specificity of the synthesized CTSE-activatable probe was verified. Quantitative determination identified that the fluorescence signal ratio of pancreatic tumor to normal pancreas gradually increased in association with progressive pathological grades, with the exception of no significant difference between PanIN-II and PanIN-III grades. Finally, we monitored pancreatic carcinogenesis in vivo using confocal laser endomicroscopy (CLE) in combination with the CTSE-activatable probe. A prospective double-blind control study was performed to evaluate the accuracy of this method in diagnosing PDAC and PanINs of all grades (>82.7%). This allowed us to establish effective diagnostic criteria for CLE in PDAC and PanINs to facilitate the monitoring of PDAC in high-risk populations.
    PLoS ONE 09/2014; 9(9):e106566. DOI:10.1371/journal.pone.0106566 · 3.23 Impact Factor
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    ABSTRACT: Background: Pancreas-cancer prognosis is dismal, with 5-year survival less than 5%. Significant relationships between aspirin use and decreased pancreas-cancer incidence and mortality have been shown in four of 13 studies. Methods: To evaluate further a possible association between aspirin use and risk of pancreatic cancer, we used data from a population-based Connecticut study conducted from January 2005 to August 2009, of 362 pancreas-cancer cases frequency matched to 690 randomly sampled controls. Results: Overall, regular use of aspirin was associated with reduced risk of pancreatic cancer [odds ratio (OR), 0.52; 95% confidence interval (CI), 0.39-0.69]. Increments of decreasing risk of pancreatic cancer were observed for each year of low-dose or regular-dose aspirin use (OR, 0.94;95%CI, 0.91-0.98 and OR, 0.98;95%CI, 0.96-1.01, respectively) and for increasing years in the past that low-dose or regular-dose aspirin use had started (OR, 0.95; 95% CI, 0.92-0.99 and OR, 0.98; 95% CI, 0.96-1.00, respectively). Reduced risk of pancreatic cancer was seen in most categories of calendar time period of aspirin use, for both low-dose aspirin and regulardose aspirin use. Relative to continuing use at the time of interview, termination of aspirin use within 2 years of interview was associated with increased risk of pancreatic cancer (OR, 3.24; 95% CI, 1.58-6.65). Conclusions: Our results provide some support that a daily aspirin regimen may reduce risk of developing pancreatic cancer. Impact: Long-term aspirin use has benefits for both cardiovascular disease and cancer, but appreciable bleeding complications that necessitate risk-benefit analysis for individual applications.
    Cancer Epidemiology Biomarkers & Prevention 06/2014; 23(7):1254-63. DOI:10.1158/1055-9965.EPI-13-1284. · 4.13 Impact Factor

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