Clinicopathological Features of Malignant Intraductal Papillary Mucinous Tumors of the Pancreas

Kawai, Manabu; Uchiyama, Kazuhisa; Tani, Masaji; Onishi, Hironobu; Kinoshita, Hiroyuki; Ueno, Masaki; Hama, Takashi; Yamaue, Hiroki

doi:10.1001/archsurg.139.2.188

Cited by 75 publications

(61 citation statements)

References 29 publications

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“…Currently, however, there are no laboratory markers that can adequately detect IPMNs or differentiate between benign and malignant IPMNs. Conventional cytologic analysis of pancreatic tissue and serum CA19-9 levels are commonly used in the clinical setting, but they are not able to differentiate between benign and malignant IPMNs (41,42). The identification and characterization of overexpressed genes as well as underexpressed genes in IPMNs might allow us to identify clinically relevant biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Down-Regulation of CDKN1C/p57KIP2 in Pancreatic Ductal Neoplasms Identified by Gene Expression Profiling

Sato

Matsubayashi

Abe

et al. 2005

Clinical Cancer Research

103

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Purpose: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an increasingly identified precursor to infiltrating ductal adenocarcinoma. Although our knowledge of the clinical and pathologic features of IPMNs is increasing, the molecular mechanisms underlying these neoplasms remain poorly understood. Experimental Designs: To provide further insight into the molecular pathobiology of IPMNs, global expression profiling was done to determine genes that are inactivated/down-regulated in IPMNs using oligonucleotide microarrays (Affymetrix). Results: In total, 300 unique transcripts (217 known genes) were identified as highly underexpressed in 12 IPMNs (<10-fold lower and P < 0.05) compared with five normal pancreatic ductal epithelium samples obtained by laser capture microdissection. The differential expression of a selection of genes was confirmed using reverse-transcription PCR. One of the genes underexpressed at both the transcriptional and protein level in a significant proportion of IPMNs was the cyclin-dependent kinase inhibitor, CDKN1C/p57KIP2. CDKN1C expression was also decreased in many pancreatic cancer cell lines and was restored following treatment with a DNA methylation inhibitor (5-aza-2V -deoxycitidine) or, more potently, with a histone deacetylase inhibitor (trichostatin A). Partial methylation of the CDKN1C promoter CpG island was found in most, but not all, pancreatic cancer cell lines with reduced CDKN1C expression, and was also detectable in IPMNs. Furthermore, a subset of pancreatic cancers showed complete hypomethylation of LIT1, an imprinting control region important for the regulation of CDKN1C expression. Complete hypomethylation in these cancers was the result of deletion of the methylated LIT1 allele at 11p15.5 rather than loss of imprinting. Conclusions: These findings suggest that CDKN1C is commonly down-regulated in pancreatic ductal neoplasms through a combination of promoter hypermethylation, histone deacetylation, and loss of the maternal allele expressing CDKN1C. Intraductal papillary mucinous neoplasm (IPMN) is anincreasingly recognized noninvasive cystic neoplasm of the pancreas that is characterized by unique clinical, pathologic, and molecular features (1 -8). Although most IPMNs are slowgrowing and less aggressive compared with conventional ductal adenocarcinoma, early and accurate diagnosis of IPMNs is important because an associated infiltrating adenocarcinoma is frequently identified in the pancreas affected by IPMNs, suggesting that IPMNs evolve into invasive ductal adenocarcinomas (2, 7, 9 -11). Recent evidence also suggests that many individuals with an inherited susceptibility to develop pancreatic ductal adenocarcinoma may initially develop IPMNs prior to developing pancreatic adenocarcinoma. In this regard, two recently completed studies have undertaken the screening of asymptomatic individuals at high risk for developing pancreatic neoplasia using endoscopic ultrasound and computed tomography scanning of the pancreas. The first study identified ...

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Section: Discussionmentioning

confidence: 99%

Epigenetic Down-Regulation of CDKN1C/p57KIP2 in Pancreatic Ductal Neoplasms Identified by Gene Expression Profiling

Sato

Matsubayashi

Abe

et al. 2005

Clinical Cancer Research

103

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“…Sohn et al [22] reported that there appears to be a lag time of approximately 5 years in the progression from adenoma to invasive carcinoma and that progression to invasive carcinoma occurs relatively quickly once moderate dysplasia is found. Kawai et al [17] reported that the malignancy rate of IPMNs was 48% while it was 67% in the study conducted by Lopez Hänninen et al [23] . In our study, the malignancy rate was 60% (12 of 20).…”

Section: Discussionmentioning

confidence: 94%

“…The IPMN can evolve through all biological stages, from slight dysplasia to carcinoma. As one of the few surgically curable pancreatic tumors, accurate preoperative prediction of malignancy remains one of the major issues in the optimal treatment of IPMNs, and it also influences the outcome of the resection [16,17] . The present study retrospectively assessed the imaging findings of IPMNs with MDCT and evaluated the capabilities of MDCT with emphasis on the postprocessing techniques to predict the malignancy of IPMNs.…”

Section: Introductionmentioning

confidence: 99%

Imaging features of intraductal papillary mucinous neoplasms of the pancreas in multi-detector row computed tomography

Tan

Ya-e²,

Wang³

et al. 2009

WJG

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AIM:To retrospectively evaluate the imaging features of pancreatic intraductal papillary mucinous neoplasms (IPMNs) in multi-detector row computed tomography (MDCT). METHODS:A total of 20 patients with pathologicallyconfirmed intraductal papillary mucinous neoplasms (IPMNs) were included in this study. Axial MDCT images combined with CT angiography (CTA) and multiplanar volume reformations (MPVR) or curved reformations (CR) were preoperatively acquired. Two radiologists (Tan L and Wang DB) reviewed all the images in consensus using an interactive picture archiving and communication system. The disputes in readings were resolved through consultation with a third experienced radiologist (Chen KM). Finally, the findings and diagnoses were compared with the pathologic results. RESULTS:The pathological study revealed 12 malignant IPMNs and eight benign IPMNs. The diameters of the cystic lesions and main pancreatic ducts (MPDs) were significantly larger in malignant IPMNs compared with those of the benign IPMNs (P < 0.05). The combinedtype IPMNs had a higher rate of malignancy than the other two types of IPMNs (P < 0.05). Tumors with mural nodules and thick septa had a significantly higher incidence of malignancy than tumors without these features (P < 0.05). Communication of side-branch IPMNs with the MPD was present in nine cases at pathologic examination. Seven of them were identified from CTA and MPVR or CR images. From comparison with the pathological diagnosis, the sensitivity, specificity, and accuracy of MDCT in characterizing the malignancy of IPMN of the pancreas were determined to be 100%, 87.5% and 95%, respectively.

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“…The diagnostic accuracy of CCR7 expression with regard to the presence of lymph node metastases was quantified via a receiver operating characteristic (ROC) analysis (24,25). The associations between CCR7 expression and clinicopathological features were evaluated by either the ¯2 test or Fisher's exact test as appropriate.…”

Section: Discussionmentioning

confidence: 99%

High CCR7 mRNA expression of cancer cells is associated with lymph node involvement in patients with esophageal squamous cell carcinoma

Iwahashi¹

2009

Int J Oncol

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Abstract. Esophageal squamous cell carcinoma (SCC) is one of the biological malignant tumors. Once a tumor invades the submucosa, an incidence of lymph node (LN) metastases is very high, thus resulting in poor survival. Recently, chemokines have been reported to play an important role in organspecific metastases in several malignancies. In particular, CCR7 has been reported to be associated with LN metastases by immunohistochemistry. However, there have been no studies of quantitative analyses of CCR7 mRNA expression on cancer cells. In this study, we investigated the clinical significance of the expression of CCR7 in the establishment of LN metastases of esophageal SCC. A series of 78 patients with esophageal SCC who underwent esophagectomy were consecutively selected. The expression of CCR7 mRNA from tumor tissue samples was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), and that from cancer cell samples collected using laser microdissection system was analyzed by qRT-PCR. Immunohistochemical staining of CCR7 was also performed. Although CCR7 mRNA expression in tumor tissues demonstrated no association with the LN metastases, that in cancer cells correlated with LN metastases (p<0.05) due to the fact that not only cancer cells but also infiltrating lymphocytes expressed CCR7 in tumor tissue. Multivariate logistic regression analysis revealed a high CCR7 expression in cancer cells to be an independent predictive factor for LN metastases. These results suggested that CCR7 expression might play an important role in establishing LN metastases in patients with esophageal SCC.

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Clinicopathological Features of Malignant Intraductal Papillary Mucinous Tumors of the Pancreas

Abstract: Background: The accurate differential diagnosis of malignant intraductal papillary mucinous tumors (IPMTs) of the pancreas from benign IPMTs remains unclear. Hypothesis: Predictive factors for differentiating malignant IPMTs from benign IPMTs can be documented.

Cited by 75 publications

References 29 publications

Epigenetic Down-Regulation of CDKN1C/p57KIP2 in Pancreatic Ductal Neoplasms Identified by Gene Expression Profiling

Epigenetic Down-Regulation of CDKN1C/p57KIP2 in Pancreatic Ductal Neoplasms Identified by Gene Expression Profiling

Imaging features of intraductal papillary mucinous neoplasms of the pancreas in multi-detector row computed tomography

High CCR7 mRNA expression of cancer cells is associated with lymph node involvement in patients with esophageal squamous cell carcinoma

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