Histologic characteristics of pancreatic intraepithelial neoplasia associated with different pancreatic lesions

Recavarren, Claudia; Labow, Daniel M.; Liang, Jane; Zhang, Lanjing; Wong, Melisa L.; Zhu, Hongfa; Wang, Jinhua; Francis, Franto; Xu, Ruliang

doi:10.1016/j.humpath.2010.05.022

Cited by 31 publications

(27 citation statements)

References 37 publications

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“…That was acknowledged by Stelow et al [37] and, very recently, by Recavarren et al [38]. However, the average age of patients with NENs included in those reports was above 45 years; that is, they were in significant proportion older than patients with NENs included in the present study.…”

Section: Discussionmentioning

confidence: 47%

“…Several groups of investigators studied the prevalence of PC precursor lesions in patients without clinically detectable pancreatic diseases and/or patients with different types of tumors of non-ductal origin [21, 23, 29, 37, 38, 49–51]. …”

Section: Discussionmentioning

confidence: 99%

“…That control group was established since it is highly probable that the prevalence of PC precursor lesions in patients with NENs represent their “baseline” prevalence in the general population. It was showed previously that the prevalence of PC precursor lesions in patients with NENs is primarily related to the patients’ age and/or presence of chronic pancreatitis [37, 38]. Moreover, there is no convincing evidence that NENs are related pathogenetically to PanINs/IPMNs [35].…”

Section: Methodsmentioning

confidence: 99%

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Precursor lesions of early onset pancreatic cancer

et al. 2011

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Early onset pancreatic cancer (EOPC) constitutes less than 5% of all newly diagnosed cases of pancreatic cancer (PC). Although histopathological characteristics of EOPC have been described, no detailed reports on precursor lesions of EOPC are available. In the present study, we aimed to describe histopathological picture of extratumoral parenchyma in 23 cases of EOPCs (definition based on the threshold value of 45 years of age) with particular emphasis on two types of precursor lesions of PC: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs). The types, grades, and densities of precursor lesions of PC were compared in patients with EOPCs, in young patients with neuroendocrine neoplasms (NENs), and in older (at the age of 46 or more) patients with PC. PanINs were found in 95.6% of cases of EOPCs. PanINs-3 were found in 39.1% of EOPC cases. Densities of all PanIN grades in EOPC cases were larger than in young patients with NENs. Density of PanINs-1A in EOPC cases was larger than in older patients with PC, but densities of PanINs of other grades were comparable. IPMN was found only in a single patient with EOPC but in 20% of older patients with PC. PanINs are the most prevalent precursor lesions of EOPC. IPMNs are rarely precursor lesions of EOPC. Relatively high density of low-grade PanINs-1 in extratumoral parenchyma of patients with EOPC may result from unknown multifocal genetic alterations in pancreatic tissue in patients with EOPCs.

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Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Precursor lesions of early onset pancreatic cancer

et al. 2011

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“…The concurrent loss of zinc, ZIP3, and REBB-1 is evident in the early stage PanIN epithelium and persists though the PanIN transformation to the putative invasive ductal adenocarcinoma cells and ultimately persists in early stage malignancy through the advanced stage malignancy. A prevailing view is that PanINs, especially PanIN 2 and PanIN 3, are precancer lesions that give rise to ductal adenocarcinoma (for reviews, see [3–5]). Scarlett et al [3] have presented the concept of the involvement of PanIN lesions in the transformation of normal ductal epithelium to ductal adenocarcinoma, which is shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…As such, one could expect that the decrease in zinc and the downregulation of ZIP3 and RREB-1 will be evident in premalignant cells/lesions that lead to the development of malignant cells. Presently, pancreatic intraepithelial neoplasia (PanIN) is considered to be precancerous lesions that give rise to the malignant cells [3–5]. …”

Section: Introductionmentioning

confidence: 99%

Evidence for Changes in RREB-1, ZIP3, and Zinc in the Early Development of Pancreatic Adenocarcinoma

Costello

Zou

Desouki

et al. 2012

J Gastrointest Canc

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Purpose Pancreatic adenocarcinoma is an untreatable cancer with a 5-year survival rate of about 6 % or less for the past 35 years. This lack of significant progress is largely due to the lack of elucidation and understanding of the factors involved in the development of this cancer. Recent studies identified and implicated zinc in the development and progression of pancreatic cancer. This study was conducted to establish the changes in zinc, ZIP3 zinc transporter, and Ras-responsive element-binding protein 1 (RREB-1) transcription factor as early events in the development of malignancy. Methods In situ relative zinc determination and immunohistochemical analysis of ZIP3 and RREB-1 were performed on archived human pancreatic tissue sections and tissue micro-arrays. Normal/benign versus adenocarcinoma pancreas was compared. Panc1 cells were employed to determine the influence of RREB-1 on ZIP3 expression. Results Zinc levels of normal ductal and acinar epithelium were markedly and consistently decreased in adenocarcinoma. Pancreatic intraepithelial neoplasia (PanIN) lesions also exhibited a loss of zinc. ZIP3 and RREB-1 were also markedly downregulated. Initial results indicate that RREB-1 regulates ZIP3 expression. Conclusions These results corroborate the earlier report that zinc, ZIP3, and RREB-1 are markedly decreased in early stage adenocarcinoma. Additionally and most importantly, these changes occur in PanIN, which are thought to be precancerous lesions leading to ductal adenocarcinoma. These results support a concept that downregulation of RREB-1 causes downregulation of ZIP3, which results in decreased zinc in premalignant and carcinoma cells. The decrease in zinc is essential to remove its cytotoxic effects on malignant cells. This relationship constitutes a new concept of early genetic/metabolic events in the progressive transformation of normal cells to premalignant cells to malignant cells in the development of pancreatic cancer.

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