Pancreatic Intraepithelial Neoplasia

Hruban, Ralph H.; Brune, Kieran; Fukushima, Noriyoshi; Maitra, Anirban

doi:10.1007/978-0-387-69252-4_3

Cited by 124 publications

(166 citation statements)

References 49 publications

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“…Preinvasive PanIN lesions are the most common precursors to invasive PDAC, rendering them promising targets for diagnosis and intervention, especially in the high-risk population (30). Using CFL in combination with an established cathepsin-activatable NIRF probe allowed us to distinguish between different grades of mPanIN lesions by signal intensity, cellular morphology, and pattern of activation.…”

Section: Discussionmentioning

confidence: 99%

In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging

Eser

Messer²,

Eser³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor patient outcome often resulting from late diagnosis in advanced stages. To date methods to diagnose early-stage PDAC are limited and in vivo detection of pancreatic intraepithelial neoplasia (PanIN), a preinvasive precursor of PDAC, is impossible. Using a cathepsin-activatable near-infrared probe in combination with flexible confocal fluorescence lasermicroscopy (CFL) in a genetically defined mouse model of PDAC we were able to detect and grade murine PanIN lesions in real time in vivo. Our diagnostic approach is highly sensitive and specific and proved superior to clinically established fluorescein-enhanced imaging. Translation of this endoscopic technique into the clinic should tremendously improve detection of pancreatic neoplasia, thus reforming management of patients at risk for PDAC. is one of the deadliest human malignancies, with an extremely poor 5-y survival rate below 5% (1). Because patients generally present with symptoms relating to late stages of the disease, diagnosis of resectable PDAC is achieved in less than 15% of cases (1). However, investigators have reported that diagnosis and resection of early-stage PDAC (<2 cm in size) can result in a 4-y survival rate of up to 78% (2-5). These data suggest that early detection of PDAC can improve patient outcome. In addition, it has been shown that resection of PDAC combined with adjuvant chemotherapy can improve 5-y survival rates to 25%. Thus, increasing the chance of resection will lead to improved survival.Of the more than 33,000 new cases of PDAC diagnosed in the United States every year, ∼10% occur in families with a high prevalence of PDAC and are thus referred to as familial (6, 7). In a cohort study of twins, it was proposed that inherited factors may be responsible for up to 36% of pancreatic cancers, suggesting that the incidence of familial pancreatic cancer may be even higher than presently assumed (8). To date, several conditions associated with familial PDAC have been described and groups of individuals at low, moderate, or high risk for developing the disease have been defined (9, 10). Although clinical trials are currently testing screening protocols for the high-risk group, aimed at detecting curable precursors of PDAC such as intraductal papillary mucinous neoplasia, pancreatic intraepithelial neoplasia (PanIN), and early-stage PDAC (10-12), the results of these trials show that early lesions are often missed. Furthermore, false positive findings can lead to overtreatment of a significant fraction of the screened population (12). These findings show that better diagnostic tools for the detection of preneoplastic lesions and early-stage PDAC are urgently needed. Recent data demonstrate that preinvasive precursors progress slowly over many years to decades to invasive pancreatic cancer (13). The parental pancreatic cancer founder clone then requires more than 5 y to acquire the capacity to metastasize (13). Thus, there is a time frame of several years for the diagnosi...

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Section: Discussionmentioning

confidence: 99%

In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging

Eser

Messer²,

Eser³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This study assessed the impact of preneoplastic lesion pattern and histo-morphological features of characteristics and molecular mechanisms have rapidly evolved, leading to new classification of preneoplastic lesions (8). Notwithstanding, the relationship between these findings and the clinical setting is not obvious yet.…”

Section: Discussionmentioning

confidence: 99%

“…A continuum of lesions may be observed between normal parenchyma and adenocarcinoma (4)(5)(6)(7). The most frequent preneoplastic lesions that usually precede pancreatic adenocarcinoma are subdivided into two types: pancreatic intraepithelial neoplasia (PanINs) and intracanalar papillary mucinous neoplasia (IPMN) (8)(9)(10)(11). The former is a peripheral lesion affecting small pancreatic ducts (< 5mm in diameter), which is often described, in ductal adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic adenocarcinoma: the impact of preneoplastic lesion pattern on survival

Flattet¹,

Yamaguchi²,

Andrejevic‐Blant³

et al. 2015

BST

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“…Pancreatic cancer most commonly develops through a series of intraductal epithelial lesions called pancreatic intraepithelial neoplasms (PanIN) [4], where minimally dysplastic epithelium progresses to more severe dysplasia and finally to invasive carcinoma with the successive accumulation of genetic mutations. The molecular events include the activation of the KRAS oncogene, inactivation of the CDKN2A tumour suppressor gene (p16 INK4A ), and mutation and/or inactivation of TP53 and SMAD4 tumour suppressor genes.…”

Section: Molecular Pathology Of Pancreatic Cancermentioning

confidence: 99%

Understanding pancreatic cancer genomes

Cowley

Chang

Johns

et al. 2013

J Hepato Biliary Pancreat

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Pancreatic cancer is the fourth leading cause of cancer death in our society, with a mortality that virtually parallels its incidence, a median survival of \12 months even with maximal therapy, and a 5-year survival rate of \5 %. The diversity of clinical outcomes and the molecular heterogeneity of histopathologically similar cancer types, incomplete knowledge of the genomic aberrations that drive carcinogenesis and the lack of therapeutics that specifically target most known genomic aberrations necessitates large-scale detailed analysis of cancer genomes to identify novel potential therapeutic strategies.

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Pancreatic Intraepithelial Neoplasia

Cited by 124 publications

References 49 publications

In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging

In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging

Pancreatic adenocarcinoma: the impact of preneoplastic lesion pattern on survival

Understanding pancreatic cancer genomes

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