Pathology Analysis Reveals That Dysplastic Pancreatic Ductal Lesions Are Frequent in Patients With Hereditary Pancreatitis

Rebours, Vinciane; Lévy, Philippe; Mosnier, Jean‐François; Scoazec, Jean‐Yves; Soubeyrand, Marie-Sophie; Fléjou, Jean‐François; Turlin, Bruno; Hammel, Pascal; Ruszniewski, Philippe; Bédossa, Pierre; Couvelard, Anne

doi:10.1016/j.cgh.2009.09.009

Cited by 43 publications

(22 citation statements)

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“…33 Overall, PanINs increase in frequency as a function of age, similar to SCOUTs and (in more recent reports) p53 signatures. 4,12,13,26,31,34,35 Currently used methods of assessing PanIN frequency are by either measuring the number of PanINs per cm 2 of pancreatic tissue 19,20,36 or by measuring PanIN frequency per slide. 32 The first method measures both epithelium and parenchyme within the studied fields and as such measuring errors may occur when comparing the frequency of PanINs in fields with a variable epithelial/parenchymal ratio.…”

Section: Discussionmentioning

confidence: 99%

“…However, resolving the importance of these disparate events requires attention to confounding variables such as age and equally important, the intrinsic sampling variation across different tissue sections, each with presumably different amounts of epithelium. 14 Numerous examples in the literature attest to the importance of ascertaining precursor frequency or size as a surrogate for cancer risk, such as in the colon, pancreas and prostate, [15][16][17][18][19][20][21][22][23][24] These organs house early epithelial changes that are not unlike the SCOUTs described in the fallopian tube. As high precursor frequencies could signal an acquired or underlying familial tendency for cancer development, precise quantification of the epithelial perimeter at risk is paramount.…”

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Digital quantification of precursor frequency in the fallopian tube and its significance

et al. 2012

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A high frequency of precursor lesions is a risk factor for cancer in many organ systems but must be precisely quantified. Pelvic serous neoplasia is associated with an estimated increase in frequency of secretory cell outgrowths (SCOUTs) with loss of PAX2 protein (PAX2p) expression (PAX2p-null SCOUTs) in the fallopian tube. However, to confirm this, PAX2p-null SCOUTs must be precisely quantified relative to the epithelial surface. We developed a method by which fallopian tube sections were digitized using an iScan brightfield scanner (BioImagene) and uploaded in Adobe Photoshop CS3 Extended. Pixel length was translated into microns and epithelial length measured with the Magic Wand tool. SCOUTs were expressed as a function of total epithelial perimeter. Frequency, required perimeter length, topographic clustering tendency and effects of age were ascertained. SCOUT frequency per 10 cm was 0-4.60 for cases and 0-1.66 for controls, averaging 0.84 and 0.27, respectively, (P ¼ 0.007). Required perimeter length for SCOUT detection was less in serous cancer cases and topographic distribution followed a random pattern without aberrant clustering. Age was also associated with SCOUT frequency (P ¼ 0.025) and differences between cancers and controls were still significant after adjusting for age (P ¼ 0.001). We describe an efficient method for quantifying epithelial perimeter in the fallopian tube and verify its relevance to precursor frequency. This has important implications for assessing precursor frequency both in the fallopian tube and in other organs-such as prostate, pancreas and colon-where epithelial precursors are integral to carcinogenesis. Modern Pathology (2012) 25, 1654-1661; doi:10.1038/modpathol.2012.100; published online 6 July 2012 Keywords: fallopian tube; precancer; secretory cell; serous cancer Although traditionally presumed to originate primarily in the ovarian cortex, high-grade ovarian cancers, specifically serous cancers, have been reassessed based on recent observations in the fallopian tube. 1 These include the frequent discovery of early serous cancers-termed tubal intraepithelial carcinomas-in the tubal fimbriae of women undergoing risk reducing salpingo-oophorectomy for germ-line BRCA1 or BRCA2 mutations, the observation of similar early cancers in 35-60% of un-selected women with fully developed pelvic serous cancer, and the description of a precursor condition in benign tubal mucosa with altered TP53 expression, termed the 'p53 signature'. 2-10 The latter has focused attention on the early molecular changes that may occur before the onset of either tubal intraepithelial or invasive serous carcinoma in the fallopian tube. Although the p53 signature, by virtue of its location (fimbria), p53 staining, evidence of DNA damage and proximity to intraepithelial carcinomas, is a presumptive direct precursor to intraepithelial carcinoma, a range of other discrete epithelial cell expansions have been described, termed secretory cell outgrowths or SCOUTs. [11][12][13] SCOUTs share with p53 signatures a...

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Digital quantification of precursor frequency in the fallopian tube and its significance

et al. 2012

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“…This strong association between NP with inflammation determined to evaluate the expression and activity of this protein in PDAC, specifically in patients with antecedent inflammatory conditions like chronic pancreatitis, and pancreatic intraepithelial neoplasia (PanIN) (Rebours et al, 2010). Therefore, this correlation makes NP levels quantification to be a useful marker for surveillance progression from inflammation to PDAC.…”

Section: Pancreatic Juice Biomarkersmentioning

confidence: 99%

Novel Biomarkers in Pancreatic Cancer

Dima¹,

Tănase²,

Albulescu³

et al. 2012

Pancreatic Cancer - Clinical Management

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“…PDAC is often a consequence of this condition [56,57] insomuch so resected pancreata from patients with HP frequently demonstrated PanIN-3 lesions (50%) [58] . Patients with hereditary pancreatitis have a 53 to 87-fold increase risk [57,59] with an age of onset at 50 years in smokers [60] .…”

Section: Hereditary Pancreatitismentioning

confidence: 99%

Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer

Lami

Biagini

Galli

2014

WJGE

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Pancreatic cancer is a highly lethal disease with a genetic susceptibility and familial aggregation found in 3%-16% of patients. Early diagnosis remains the only hope for curative treatment and improvement of prognosis. This can be reached by the implementation of an intensive screening program, actually recommended for individuals at high-risk for pancreatic cancer development. The aim of this strategy is to identify premalignant precursors or asymptomatic pancreatic cancer lesions, curable by surgery. Endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA) seems to be the most promising technique for early detection of pancreatic cancer. It has been described as a highly sensitive and accurate tool, especially for small and cystic lesions. Pancreatic intraepithelial neoplasia, a precursor lesion which is highly represented in highrisk individuals, seems to have characteristics chronic pancreatitis-like changes well detected by EUS. Many screening protocols have demonstrated high diagnostic yields for pancreatic pre-malignant lesions, allowing prophylactic pancreatectomies. However, it shows a high interobserver variety even among experienced endosonographers and a low sensitivity in case of chronic pancreatitis. Some new techniques such as contrast-enhanced harmonic EUS, computer-aided diagnostic techniques, confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA, promise improvement of the diagnostic yield of EUS. As the resolution of imaging improves and as our knowledge of precursor lesions grows, we believe that EUS could become the most suitable method to detect curable pancreatic neoplasms in correctly identified asymptomatic at-risk patients.© 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Endoscopic ultrasonography; Pancreatic cancer; SurveillanceCore tip: In the era of early diagnosis and screening programs, endoscopic ultrasound (EUS) represents the most promising tool able to identify pancreatic precursor neoplasms in high risk individuals. If compared to other imaging techniques, it is highly accurate to diagnose small pancreatic cancer and pre-malignant lesions, with very low rate of complications and limitations. Here are reported the current role of EUS in various international screening programs and its future possible developments.

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Pathology Analysis Reveals That Dysplastic Pancreatic Ductal Lesions Are Frequent in Patients With Hereditary Pancreatitis

Cited by 43 publications

References 45 publications

Digital quantification of precursor frequency in the fallopian tube and its significance

Digital quantification of precursor frequency in the fallopian tube and its significance

Novel Biomarkers in Pancreatic Cancer

Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer

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