Precursor lesions of early onset pancreatic cancer

Liszka, Łukasz; Pająk, Jacek; Mrowiec, Sławomir; Zielińska-Pająk, Ewa; Gołka, Dariusz; Lampe, Paweł

doi:10.1007/s00428-011-1056-3

Cited by 14 publications

(9 citation statements)

References 52 publications

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“…In addition, high grade PanIN synchronous with pancreatic cancer has been associated with recurrent disease after pancreatic cancer resection 29 . PanIN seems to be especially common in patients with early onset PDAC and was found in 96% of cases in one series 30 . Previous work has shown that the majority of high-grade PanIN lesions occur directly adjacent to the adenocarcinoma but lower grade lesions occurred more sporadically throughout the tissue 31 .…”

Section: Discussionmentioning

confidence: 86%

Absence of Pancreatic Intraepithelial Neoplasia Predicts Poor Survival After Resection of Pancreatic Cancer

Hassid¹,

Lucas

Salomao

et al. 2014

Pancreas

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Objectives Pancreatic intraepithelial neoplasia (PanIN), thought to represent the dominant precursor of pancreatic adenocarcinoma (PDAC), is often found synchronously adjacent to resected PDAC tumors. However, its prognostic significance on outcome following PDAC resection is unknown. Methods A total of 342 patients who underwent resection for PDAC between 2005 and 2010 at a single institution were identified and stratified according to highest grade of PanIN demonstrated surrounding the tumor. Clinical and pathologic characteristics of each patient and tissue were recorded and analyzed. The primary outcome was length of survival following resection. Results An absence of PanIN lesions was identified in 32 cases (9%), low grade PanIN without synchronous high grade lesions was identified in 52 cases (15%), and high grade PanIN was found in 258 cases (75%). Median survival in the non-PanIN group was 12.8 months, 26.3 months for the low grade PanIN group, and 23.8 months for the high grade PanIN groups (P=.043). In multivariable analysis, absence of PanIN was independently associated with poor survival (P= .002). Conclusions The patients who demonstrate an absence of PanIN in the pancreatic tissue adjacent to the resected PDAC tumor have shorter post-resection survival compared to those who demonstrate a PanIN lesion.

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Section: Discussionmentioning

confidence: 86%

Absence of Pancreatic Intraepithelial Neoplasia Predicts Poor Survival After Resection of Pancreatic Cancer

Hassid¹,

Lucas

Salomao

et al. 2014

Pancreas

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“…An aspect that argues against mAFLs being small cancers is that they retain a lobular arrangement, whereas PDAC, even if small, is characterized by a haphazard distribution of the neoplastic glands ( Figure 5A). Second, the concept of AFLs as precursors of PDAC in this mouse model does not intend to deny the PanIN-PDAC sequence, whose validity has certainly been proven for humans [3,4,8,32]. Instead, we suggest that AFLs represent an additional form of precursor lesion, which can integrate the classical PanIN-PDAC pathway in the KP mouse model.…”

Section: Aichler Et Almentioning

confidence: 85%

Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues

Aichler

Seiler

Tost

et al. 2012

The Journal of Pathology

116

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Pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions, pancreatic intraepithelial neoplasia (PanIN), display a ductal phenotype. However, there is evidence in genetically defined mouse models for PDAC harbouring a mutated kras under the control of a pancreas-specific promoter that ductal cancer might arise in the centroacinar-acinar region, possibly through a process of acinar-ductal metaplasia (ADM). In order to further elucidate this model of PDAC development, an extensive expression analysis and molecular characterization of the putative and already established (PanIN) precursor lesions were performed in the Kras(G12D/+) ; Ptf1a-Cre(ex1/+) mouse model and in human tissues, focusing on lineage markers, developmental pathways, cell cycle regulators, apomucins, and stromal activation markers. The results of this study show that areas of ADM are very frequent in the murine and human pancreas and represent regions of increased proliferation of cells with precursor potential. Moreover, atypical flat lesions originating in areas of ADM are the most probable precursors of PDAC in the Kras(G12D/+); Ptf1a-Cre(ex1/+) mice and similar lesions were also found in the pancreas of three patients with a strong family history of PDAC. In conclusion, PDAC development in Kras(G12D/+); Ptf1a-Cre(ex1/+) mice starts from ADM and a similar process might also take place in patients with a strong family history of PDAC.

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“…24,25 In one proposed model, PAX2-null secretory outgrowths are increased in frequency in the fallopian tubes of women with high-grade serous cancer yet are separable geographically by their TP53 mutation status, association with DNA damage and location ( Figure 6). Further analysis of SCOUTs for these and other gene perturbations might yield new insights into the pathogenesis of serous cancer.…”

Section: Discussionmentioning

confidence: 99%

PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer

et al. 2012

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With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. We recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct are increased in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null). The present study examined the relationship of PAX2-null SCOUTs to high-grade serous cancers by comparing oviducts from women with benign gynecologic conditions and high-grade serous cancers. PAX2-null SCOUTs were identified by immunostaining and computed as a function of location, frequency (F) per number of cross-sections examined, and age. Six hundred thirty-nine cross-sections from 35 serous cancers (364) and 35 controls (275) were examined. PAX2-null SCOUTs consisted of discrete linear stretches of altered epithelium ranging from cuboidal/columnar, to pseudostratified, the latter including ciliated differentiation. They were evenly distributed among proximal and fimbrial tubal sections. One hundred fourteen (F ¼ 0.31) and 45 (F ¼ 0.16) PAX2-null SCOUTs were identified in cases and controls, respectively. Mean individual case-specific frequencies for cases and controls were 0.39 and 0.14, respectively. SCOUT frequency increased significantly with age in both groups (P ¼ 0.01). However, when adjusted for age and the number of sections examined, the differences in frequency between cases and controls remained significant at P ¼ 0.006. This study supports a relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer. We propose a unique co-variable in benign oviductal epithelium-the PAX2-null SCOUT-that reflects underlying dysregulation in genes linked to serous neoplasia.

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Precursor lesions of early onset pancreatic cancer

Cited by 14 publications

References 52 publications

Absence of Pancreatic Intraepithelial Neoplasia Predicts Poor Survival After Resection of Pancreatic Cancer

Absence of Pancreatic Intraepithelial Neoplasia Predicts Poor Survival After Resection of Pancreatic Cancer

Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues

PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer

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