Screening for Early Pancreatic Neoplasia in High-Risk Individuals: A Prospective Controlled Study

Canto, Marcia Irene; Goggins, Michael; Hruban, Ralph H.; Petersen, Gloria M.; Giardiello, Francis M.; Yeo, Charles J.; Fishman, Elliott K.; Brune, Kieran; Axilbund, Jennifer E.; Griffin, Constance A.; Ali, Syed Z.; Richman, Jeffrey M.; Jagannath, Sanjay; Kantsevoy, Sergey V.; Kalloo, Anthony N.

doi:10.1016/j.cgh.2006.02.005

Cited by 464 publications

(259 citation statements)

References 48 publications

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“…miRNAs are shorter than coding mRNAs, and therefore more resistant to ribonuclease degradation, thus remaining amenable to quantitative measurement not only in archival tissues, but also in serum [52]. One example of such an at risk cohort would be asymptomatic individuals from high-risk familial pancreatic cancer kindreds that are undergoing endoscopic screening for early disease [53,54]; many of these patients harbor multi-focal PanINs (including high-grade lesions) or IPMNs in their pancreata [55], and miR-155 expression in the pancreatic juice might provide a diagnostic adjunct in cases borderline for malignancy. In this context, miR-21, whose expression appears to be restricted to PanIN-3 lesions, might prove an even more specific biomarker for lesions at highest risk of progression to invasive cancer.…”

Section: Discussionmentioning

confidence: 99%

Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma

Ryu

Hong²,

Karikari³

et al. 2010

Pancreatology

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118

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Background/Aims: Pancreatic intraepithelial neoplasia (PanIN) is the most common noninvasive precursor to invasive pancreatic adenocarcinoma. Misexpression of microRNAs (miRNAs) is commonly encountered in invasive neoplasia; however, miRNA abnormalities in PanIN lesions have not been documented. Methods: Three candidate miRNAs (miR-21, miR-155, and miR-221) previously reported as overexpressed in pancreatic cancers were assessed in 31 microdissected PanINs (14 PanIN-1, 9 PanIN-2, 8 PanIN-3) using quantitative reverse transcription PCR (qRT-PCR). Subsequently, miR-155 was evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in PanIN tissue microarrays. Results: Relative to microdissected non-neoplastic ductal epithelium, significant overexpression of miR-155 was observed in both PanIN-2 (2.6-fold, p = 0.02) and in PanIN-3 (7.4-fold, p = 0.014), while borderline significant overexpression of miR-21 (2.5-fold, p = 0.049) was observed in PanIN-3 only. In contrast, no significant differences in miR-221 levels were observed between ductal epithelium and PanIN lesions by qRT-PCR. LNA-ISH confirmed the aberrant expression of miR-155 in PanIN-2 (9 of 20, 45%) and in PanIN-3 (8 of 13, 62%), respectively, when compared with normal ductal epithelium (0 of 10) (p < 0.01). Conclusions: Abnormalities of miRNA expression are observed in the multistep progression of pancreatic cancer, with miR-155 aberrations demonstrable at the stage of PanIN-2, and miR-21 abnormalities at the stage of PanIN-3 lesions.

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Section: Discussionmentioning

confidence: 99%

Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma

Ryu

Hong²,

Karikari³

et al. 2010

Pancreatology

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118

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“…In den Pankreasresektaten fanden sich 6 benigne IP-MN, eine PanIN-3-Läsion sowie eine maligne IPMN [12]. Die Autoren schlossen aus dieser Studie, dass ein EUS-und CTbasiertes PC-Screening in der Lage ist, si- Bei der Bewertung der o. g. Ergebnisse, insbesondere der Prävalenz der "signifikanten" Pankreasläsionen, muss immer in Betracht gezogen werden, dass es sich um kleine Kollektive hochselektierter Personen mit meist ohne nachweisbaren zum PC-prädisponierenden Gendefekt handelt.…”

Section: Hereditäre Pankreatitis Und Zystische Fibroseunclassified

Hereditäres Pankreaskarzinom

Habbe

Langer

Bartsch

2008

Chirurg

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An inherited predisposition to pancreatic cancer (PC) is prevalent in about 3% of PC cases and is currently believed to occur in three distinct clinical settings, (1) hereditary tumour predisposition syndromes with an increased risk of PC such as Peutz-Jeghers syndrome and familial atypical multiple mole melanoma, (2) hereditary pancreatitis and cystic fibrosis, in which genetically determined early-age changes of the pancreas can predispose to the development of PC, and (3) familial pancreatic cancer syndrome (FPC). According to a recent consensus conference, high-risk individuals from PC-prone families should be enrolled in board-approved, prospective, controlled screening programs at expert centres. Based on the available data, prophylactic pancreatectomy is not indicated, since the underlying causative gene defect of the FPC syndrome is still unknown and the penetrance of PC in other tumour predisposition syndromes is either low or yet undetermined. In case of the diagnosis of a PC or high-grade precursor lesions, a prophylactic extension of the resection can be considered, since patients with hereditary PC often develop multifocal pancreatic lesions.

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“…Moreover, patients with PJS are at increased risk for IPMNs and their precursors [60]. All this is a profound implication for the screening and management of pancreatic cysts in patients with PJS [61]. …”

Section: Clinical Implications Of Genetic Alterations In Pancreatic Cmentioning

confidence: 99%

The Emerging Genetic Basis and Its Clinical Implication in Pancreatic Cancer

Chen

Guo

Wang

2015

Gastrointest Tumors

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Background: Pancreatic cancer is one of the most devastating diseases without early detection, effective screening biomarkers and therapeutic treatments. In the past decades, genetic studies have indicated various genes related to this malignancy. Summary: Genetic alterations have been involved in the initiation, progression and invasion of pancreatic cancer, which might indicate promising targets for early screening, diagnosis and future intervention. Here we will review genetic changes in pancreatic cancer and analyze their correlations with several common precursors and familial syndromes. Key Message: Genetic analysis for pancreatic cancer or its precursors might help us to characterize patients into subtype individuals in the future and have significant implications for individualized treatments. Practical Implications: At present, pancreatic cancer is regarded as a disease with a wide range of genetic alterations, including germline and somatic mutations. Some genetic alterations such as KRAS, p16^CDKN2A, TP53 and SMAD4 were specifically correlated with different types of histological precursors of pancreatic cancer and some familial syndromes highly related to pancreatic cancer. Moreover, genetic changes also predict drug sensitivity and implicate novel therapeutic targets.

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Screening for Early Pancreatic Neoplasia in High-Risk Individuals: A Prospective Controlled Study

Cited by 464 publications

References 48 publications

Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma

Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma

Hereditäres Pankreaskarzinom

The Emerging Genetic Basis and Its Clinical Implication in Pancreatic Cancer

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