Distinct expression patterns of claudin‐1 and claudin‐4 in intraductal papillary–mucinous tumors of the pancreas

Tsukahara, Munetoshi; Nagai, Hideo; Kamiakito, Tomoko; Kawata, Hirotoshi; Takayashiki, Norio; Saito, Ken; Tanaka, Akira

doi:10.1111/j.1440-1827.2005.01793.x

Cited by 29 publications

(27 citation statements)

References 19 publications

(20 reference statements)

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“…Our results are consistent with a previous immunohistochemical analysis showing a positive correlation between CLDN4 protein expression and histological tumor grades in intraductal papillary mucinous neoplasms. 29 The mechanism underlying the overexpression of CLDN4 in intraductal papillary mucinous neoplasms remains unclear, but a previous study has shown an association between CLDN4 overexpression and gene hypomethylation in pancreatic cancer cells. 26 In the present study, we analyzed the relationship between CLDN4 expression and papillary subtypes of intraductal papillary mucinous neoplasms.…”

Section: Discussionmentioning

confidence: 99%

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

et al. 2011

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Claudin-4, encoding a protein for tight junction formation and function, is highly overexpressed in pancreatic ductal adenocarcinoma and is also associated with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms of the pancreas. However, the expression pattern of claudin-4 during neoplastic progression of intraductal papillary mucinous neoplasms remains unknown. Using quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffinembedded tissues from 80 patients with intraductal papillary mucinous neoplasms of different histological grades and papillary subtypes. Increased expression of claudin-4 was confirmed in all the pancreatic cancer cell lines tested as compared with normal ductal epithelial cells and fibroblast cultures. The claudin-4 expression was significantly higher in high-grade intraductal papillary mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade intraductal papillary mucinous neoplasms (adenoma) (Po0.0001). In addition, claudin-4 mRNA levels were significantly higher in intestinal-type intraductal papillary mucinous neoplasms than in non-intestinaltype intraductal papillary mucinous neoplasms based on papillary subclassification (Po0.0001). Our findings suggest that claudin-4 expression is associated with neoplastic progression of intraductal papillary mucinous neoplasms and, especially, with a distinct pathway to intestinal differentiation.

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Section: Discussionmentioning

confidence: 99%

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

et al. 2011

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“…It creates a charge-selective pore in the paracellular pathway across the epithelia and selectively restricts passage of sodium in the paracellular space. 27 Significant increase of claudin-4 has been detected in pancreatic, 22,28 prostate, 20 cervical 26 and ovarian cancers. 29 For the first time, our study detected high expression of claudin-4 in biliary tract cancers in contrast to hepatocellular carcinomas at both RNA and protein levels.…”

Section: Discussionmentioning

confidence: 99%

Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas

et al. 2006

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The recently identified claudins are dominant components of tight junctions, responsible for cell adhesion, polarity and paracellular permeability. Certain claudins have been shown to have relevance in tumor development, with some of them, especially claudin-4, even suggested as future therapeutic target. The aim of the present study was to analyze the expression of claudin-4 in the biliary tree, biliary tract cancers and hepatocellular carcinomas. A total of 107 cases were studied: 53 biliary tract cancers, 50 hepatocellular carcinomas, 10 normal liver and 10 normal extrahepatic biliary duct samples. Immunohistochemical analysis was performed on conventional specimens and on tissue microarrays as well. Claudin-4 was further investigated by Western blot analysis and real-time RT-PCR. Intense membranous immunolabeling was found for claudin-4 in all biliary tract cancers unrelated to the primary site of origin, namely intrahepatic, extrahepatic or gallbladder cancers. Normal biliary epithelium showed weak positivity for claudin-4. In contrast, normal hepatocytes and tumor cells of hepatocellular carcinomas did not express claudin-4. The results of Western immunoblot analysis and real-time RT-PCR were in correlation with the immunohistochemical findings. Cytokeratins, as CK7 (92%) and CK19 (83%) were mostly positive in biliary tract cancers, however, one-third of hepatocellular carcinomas also expressed CK7 (34%). HSA antibody (HepPar1) reacted with the majority of hepatocellular carcinomas (86%), while being positive in a low percentage of the biliary tract cancers (8%). In conclusion, this is the first report of a significantly increased claudin-4 expression in biliary tract cancers, which represents a novel feature of tumors of biliary tract origin. Claudin-4 expression seems to be a useful marker in differentiating biliary tract cancers from hepatocellular carcinomas and could well become a potential diagnostic tool.

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“…It is also shown that Claudin 1 expression induces cell growth by increasing expression of TNF-α in pancreatic cancer cell (Kondo et al, 2008). Pancreatic ductal adenocarcinomas as well as intraductal papillary mucinous tumours of the pancreas express claudins 1 and 4, and claudin 18 is present mainly in pancreatic carcinoma (Tsukahara et al, 2005;Karanjawala et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Borka et al (2007) showed expression of Claudin 1, 4 and 7 in pancreatic adenocarcinoma (Borka et al, 2007). Tsukahara et al (2005) investigated the expression of claudin-4 in human pancreas, pancreatic ductal adenocarcinomas, and intraductal papillarymucinous tumors of the pancreas (IPMT), and compared with that of claudin-1. Of 12 cases of pancreatic ductal adenocarcinoma, 11 (92%) had positive immunostaining for claudin-4, and seven (58%) for claudin-1 (Tsukahara et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Tsukahara et al (2005) investigated the expression of claudin-4 in human pancreas, pancreatic ductal adenocarcinomas, and intraductal papillarymucinous tumors of the pancreas (IPMT), and compared with that of claudin-1. Of 12 cases of pancreatic ductal adenocarcinoma, 11 (92%) had positive immunostaining for claudin-4, and seven (58%) for claudin-1 (Tsukahara et al, 2005). We found a similiar expression rate for Claudin 1 whereas Claudin 4 expression rate was found higher in our study.…”

Section: Discussionmentioning

confidence: 99%

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Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

Ali̇kanoğlu¹,

Gündüz²,

Demirpençe³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its wellknown adhesion effect.

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Distinct expression patterns of claudin‐1 and claudin‐4 in intraductal papillary–mucinous tumors of the pancreas

Cited by 29 publications

References 19 publications

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas

Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

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