Skip to main content
Top
Published in: Annals of Surgical Oncology 3/2012

01-07-2012 | Translational Research and Biomarkers

Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma

Authors: Kosuke Tsutsumi, MD, PhD, Norihiro Sato, MD, PhD, Reiko Tanabe, MD, Kazuhiro Mizumoto, MD, PhD, Katsuya Morimatsu, MD, Tadashi Kayashima, MD, Hayato Fujita, MD, PhD, Kenoki Ohuchida, MD, PhD, Takao Ohtsuka, MD, PhD, Shunichi Takahata, MD, PhD, Masafumi Nakamura, MD, PhD, Masao Tanaka, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Special Issue 3/2012

Login to get access

Abstract

Background

Identification of prognostic markers would be useful in the clinical management of patients with pancreatic ductal adenocarcinoma (PDAC). The clinical relevance of claudin-4 (CLDN4), recently identified as overexpressed in PDAC, is unknown.

Methods

Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), we analyzed CLDN4 mRNA expression in a panel of 9 pancreatic cancer cell lines and formalin-fixed paraffin-embedded (FFPE) tissues from 100 patients with PDAC. The CLDN4 expression levels were then correlated with clinicopathological variables and patient outcome. We also performed immunohistochemical analysis in 20 FFPE samples of PDAC to investigate the expression of CLDN4 protein.

Results

Increased expression of CLDN4 was confirmed in all the pancreatic cancer cell lines tested compared with normal ductal epithelial cells and fibroblasts. We found that low expression of CLDN4 was significantly associated with shorter survival in patients with PDAC (hazard ratio; 1.362, 95% confidence interval; 1.011–1.873, P = 0.0419). Patients with high CLDN4 expression survived longer for a median of 63.0 months, compared with 14.7 months in patients with low CLDN4 expression (P = 0.0067). In immunohistochemical analysis, the level of CLDN4 mRNA expression was significantly correlated with the expression of CLDN4 protein (P = 0.0168).

Conclusion

Increased expression of CLDN4 mRNA predicts better prognosis in PDAC.
Literature
1.
go back to reference Eskelinen MJ, Haglund UH. Prognosis of human pancreatic adenocarcinoma: review of clinical and histopathological variables and possible uses of new molecular methods. Eur J Surg. 1999;165:292–306.PubMedCrossRef Eskelinen MJ, Haglund UH. Prognosis of human pancreatic adenocarcinoma: review of clinical and histopathological variables and possible uses of new molecular methods. Eur J Surg. 1999;165:292–306.PubMedCrossRef
2.
go back to reference Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer. 2002;26:176–275.PubMedCrossRef Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer. 2002;26:176–275.PubMedCrossRef
3.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRef Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRef
4.
go back to reference Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.PubMedCrossRef Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.PubMedCrossRef
5.
go back to reference Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G, et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut. 2005;54:385–7.PubMedCrossRef Carpelan-Holmstrom M, Nordling S, Pukkala E, Sankila R, Luttges J, Kloppel G, et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut. 2005;54:385–7.PubMedCrossRef
6.
go back to reference Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244:10–5.PubMedCrossRef Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244:10–5.PubMedCrossRef
7.
go back to reference Ferrone CR, Finkelstein DM, Thayer SP, Muzikansky A, Fernandez-delCastillo C, Warshaw AL. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.PubMedCrossRef Ferrone CR, Finkelstein DM, Thayer SP, Muzikansky A, Fernandez-delCastillo C, Warshaw AL. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.PubMedCrossRef
8.
go back to reference Muller MW, Friess H, Koninger J, Martin D, Wente MN, Hinz U, et al. Factors influencing survival after bypass procedures in patients with advanced pancreatic adenocarcinomas. Am J Surg. 2008;195:221–8.PubMedCrossRef Muller MW, Friess H, Koninger J, Martin D, Wente MN, Hinz U, et al. Factors influencing survival after bypass procedures in patients with advanced pancreatic adenocarcinomas. Am J Surg. 2008;195:221–8.PubMedCrossRef
9.
go back to reference Kondo N, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, et al. Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2321–9.PubMedCrossRef Kondo N, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, et al. Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2321–9.PubMedCrossRef
10.
go back to reference Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, et al. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009;15:4674–9.PubMedCrossRef Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, et al. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009;15:4674–9.PubMedCrossRef
11.
go back to reference Sinicrope FA, Evans DB, Leach SD, Cleary KR, Fenoglio CJ, Lee JJ, et al. bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome. Clin Cancer Res. 1996;2:2015–22.PubMed Sinicrope FA, Evans DB, Leach SD, Cleary KR, Fenoglio CJ, Lee JJ, et al. bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome. Clin Cancer Res. 1996;2:2015–22.PubMed
12.
go back to reference Nio Y, Dong M, Iguchi C, Yamasawa K, Toga T, Itakura M, et al. Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy. J Surg Oncol. 2001;76:188–96.PubMedCrossRef Nio Y, Dong M, Iguchi C, Yamasawa K, Toga T, Itakura M, et al. Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy. J Surg Oncol. 2001;76:188–96.PubMedCrossRef
13.
go back to reference Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol. 2001;19:1118–27.PubMed Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol. 2001;19:1118–27.PubMed
14.
go back to reference Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res. 2004;10:2832–45.PubMedCrossRef Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res. 2004;10:2832–45.PubMedCrossRef
15.
go back to reference Gerdes B, Ramaswamy A, Ziegler A, Lang SA, Kersting M, Baumann R, et al. p16INK4a is a prognostic marker in resected ductal pancreatic cancer: an analysis of p16INK4a, p53, MDM2, an Rb. Ann Surg. 2002;235:51–9.PubMedCrossRef Gerdes B, Ramaswamy A, Ziegler A, Lang SA, Kersting M, Baumann R, et al. p16INK4a is a prognostic marker in resected ductal pancreatic cancer: an analysis of p16INK4a, p53, MDM2, an Rb. Ann Surg. 2002;235:51–9.PubMedCrossRef
16.
go back to reference Joo YE, Rew JS, Park CS, Kim SJ. Expression of E-cadherin, alpha- and beta-catenins in patients with pancreatic adenocarcinoma. Pancreatology. 2002;2:129–37.PubMedCrossRef Joo YE, Rew JS, Park CS, Kim SJ. Expression of E-cadherin, alpha- and beta-catenins in patients with pancreatic adenocarcinoma. Pancreatology. 2002;2:129–37.PubMedCrossRef
17.
go back to reference Niedergethmann M, Hildenbrand R, Wostbrock B, Hartel M, Sturm JW, Richter A, et al. High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas. 2002;25:122–9.PubMedCrossRef Niedergethmann M, Hildenbrand R, Wostbrock B, Hartel M, Sturm JW, Richter A, et al. High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas. 2002;25:122–9.PubMedCrossRef
18.
go back to reference Kuwahara K, Sasaki T, Kuwada Y, Murakami M, Yamasaki S, Chayama K. Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas. 2003;26:344–9.PubMedCrossRef Kuwahara K, Sasaki T, Kuwada Y, Murakami M, Yamasaki S, Chayama K. Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas. 2003;26:344–9.PubMedCrossRef
19.
go back to reference Garcea G, Neal CP, Pattenden CJ, Steward WP, Berry DP. Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer. 2005;41:2213–36.PubMedCrossRef Garcea G, Neal CP, Pattenden CJ, Steward WP, Berry DP. Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer. 2005;41:2213–36.PubMedCrossRef
20.
go back to reference Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res. 2006;66:3928–35.PubMedCrossRef Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S, et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res. 2006;66:3928–35.PubMedCrossRef
21.
go back to reference Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Fujita H, Nakata K, et al. S100A4 mRNA is a diagnostic and prognostic marker in pancreatic carcinoma. J Gastrointest Surg. 2009;13:1852–8.PubMedCrossRef Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Fujita H, Nakata K, et al. S100A4 mRNA is a diagnostic and prognostic marker in pancreatic carcinoma. J Gastrointest Surg. 2009;13:1852–8.PubMedCrossRef
22.
go back to reference Hough CD, Sherman-Baust CA, Pizer ES, Montz FJ, Im DD, Rosenshein NB, et al. Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res. 2000;60:6281–7.PubMed Hough CD, Sherman-Baust CA, Pizer ES, Montz FJ, Im DD, Rosenshein NB, et al. Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res. 2000;60:6281–7.PubMed
23.
go back to reference Long H, Crean CD, Lee WH, Cummings OW, Gabig TG. Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res. 2001;61:7878–81.PubMed Long H, Crean CD, Lee WH, Cummings OW, Gabig TG. Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res. 2001;61:7878–81.PubMed
24.
go back to reference Kominsky SL, Vali M, Korz D, Gabig TG, Weitzman SA, Argani P, et al. Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am J Pathol. 2004;164:1627–33.PubMedCrossRef Kominsky SL, Vali M, Korz D, Gabig TG, Weitzman SA, Argani P, et al. Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am J Pathol. 2004;164:1627–33.PubMedCrossRef
25.
go back to reference Ryu B, Jones J, Hollingsworth MA, Hruban RH, Kern SE. Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res. 2001;61:1833–8.PubMed Ryu B, Jones J, Hollingsworth MA, Hruban RH, Kern SE. Invasion-specific genes in malignancy: serial analysis of gene expression comparisons of primary and passaged cancers. Cancer Res. 2001;61:1833–8.PubMed
26.
go back to reference Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, et al. Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol. 2003;162:1151–62.PubMedCrossRef Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, et al. Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol. 2003;162:1151–62.PubMedCrossRef
27.
go back to reference Hewitt KJ, Agarwal R, Morin PJ. The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer. 2006;6:186.PubMedCrossRef Hewitt KJ, Agarwal R, Morin PJ. The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer. 2006;6:186.PubMedCrossRef
28.
go back to reference Michl P, Barth C, Buchholz M, Lerch MM, Rolke M, Holzmann KH, et al. Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res. 2003;63:6265–71.PubMed Michl P, Barth C, Buchholz M, Lerch MM, Rolke M, Holzmann KH, et al. Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res. 2003;63:6265–71.PubMed
29.
go back to reference Ohuchida K, Mizumoto K, Murakami M, Qian LW, Sato N, Nagai E, et al. Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Cancer Res. 2004;64:3215–22.PubMedCrossRef Ohuchida K, Mizumoto K, Murakami M, Qian LW, Sato N, Nagai E, et al. Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Cancer Res. 2004;64:3215–22.PubMedCrossRef
30.
go back to reference Bachem MG, Schneider E, Gross H, Weidenbach H, Schmid RM, Menke A, et al. Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology. 1998;115: 421–32.PubMedCrossRef Bachem MG, Schneider E, Gross H, Weidenbach H, Schmid RM, Menke A, et al. Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology. 1998;115: 421–32.PubMedCrossRef
31.
go back to reference Hruban RH, Boffetta P, Hiraoka N, et al. Ductal adenocarcinoma of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Lyon, France: IARC Press; 2010. p. 281–91. Hruban RH, Boffetta P, Hiraoka N, et al. Ductal adenocarcinoma of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Lyon, France: IARC Press; 2010. p. 281–91.
32.
go back to reference Sobin L, Wittekind C. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. In: TNM Classification of Malignant Tumors. 6th ed. New York: Wiley-Liss; 2002. Sobin L, Wittekind C. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. In: TNM Classification of Malignant Tumors. 6th ed. New York: Wiley-Liss; 2002.
33.
go back to reference Ohuchida K, Mizumoto K, Ogura Y, Ishikawa N, Nagai E, Yamaguchi K, et al. Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer. Clin Cancer Res. 2005;11:2285–92.PubMedCrossRef Ohuchida K, Mizumoto K, Ogura Y, Ishikawa N, Nagai E, Yamaguchi K, et al. Quantitative assessment of telomerase activity and human telomerase reverse transcriptase messenger RNA levels in pancreatic juice samples for the diagnosis of pancreatic cancer. Clin Cancer Res. 2005;11:2285–92.PubMedCrossRef
34.
go back to reference Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS. Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003;5:34–41.PubMedCrossRef Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS. Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003;5:34–41.PubMedCrossRef
35.
go back to reference Antonov J, Goldstein DR, Oberli A, Baltzer A, Pirotta M, Fleischmann A, et al. Reliable gene expression measurements from degraded RNA by quantitative real-time PCR depend on short amplicons and a proper normalization. Lab Invest. 2005;85:1040–50.PubMedCrossRef Antonov J, Goldstein DR, Oberli A, Baltzer A, Pirotta M, Fleischmann A, et al. Reliable gene expression measurements from degraded RNA by quantitative real-time PCR depend on short amplicons and a proper normalization. Lab Invest. 2005;85:1040–50.PubMedCrossRef
36.
go back to reference Jung H, Jun KH, Jung JH, Chin HM, Park WB. The expression of Claudin-1, Claudin-2, Claudin-3, and Claudin-4 in gastric cancer tissue. J Surg Res. 2011;167:e185–91.PubMedCrossRef Jung H, Jun KH, Jung JH, Chin HM, Park WB. The expression of Claudin-1, Claudin-2, Claudin-3, and Claudin-4 in gastric cancer tissue. J Surg Res. 2011;167:e185–91.PubMedCrossRef
37.
go back to reference Hoffmann AC, Mori R, Vallbohmer D, Brabender J, Klein E, Drebber U, et al. High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF. Neoplasia. 2008;10:674–9.PubMed Hoffmann AC, Mori R, Vallbohmer D, Brabender J, Klein E, Drebber U, et al. High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF. Neoplasia. 2008;10:674–9.PubMed
38.
go back to reference Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology. 2000;118:1001–11.PubMedCrossRef Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology. 2000;118:1001–11.PubMedCrossRef
39.
go back to reference Martin TA, Mansel RE, Jiang WG. Antagonistic effect of NK4 on HGF/SF induced changes in the transendothelial resistance (TER) and paracellular permeability of human vascular endothelial cells. J Cell Physiol. 2002;192:268–75.PubMedCrossRef Martin TA, Mansel RE, Jiang WG. Antagonistic effect of NK4 on HGF/SF induced changes in the transendothelial resistance (TER) and paracellular permeability of human vascular endothelial cells. J Cell Physiol. 2002;192:268–75.PubMedCrossRef
40.
go back to reference Ren J, Hamada J, Takeichi N, Fujikawa S, Kobayashi H. Ultrastructural differences in junctional intercellular communication between highly and weakly metastatic clones derived from rat mammary carcinoma. Cancer Res. 1990;50:358–62.PubMed Ren J, Hamada J, Takeichi N, Fujikawa S, Kobayashi H. Ultrastructural differences in junctional intercellular communication between highly and weakly metastatic clones derived from rat mammary carcinoma. Cancer Res. 1990;50:358–62.PubMed
41.
go back to reference Rajasekaran SA, Palmer LG, Quan K, Harper JF, Ball WJ Jr, Bander NH, et al. Na,K-ATPase beta-subunit is required for epithelial polarization, suppression of invasion, and cell motility. Mol Biol Cell. 2001;12:279–95.PubMed Rajasekaran SA, Palmer LG, Quan K, Harper JF, Ball WJ Jr, Bander NH, et al. Na,K-ATPase beta-subunit is required for epithelial polarization, suppression of invasion, and cell motility. Mol Biol Cell. 2001;12:279–95.PubMed
42.
go back to reference Hsueh C, Chang YS, Tseng NM, Liao CT, Hsueh S, Chang JH, et al. Expression pattern and prognostic significance of claudins 1, 4, and 7 in nasopharyngeal carcinoma. Hum Pathol. 2010;41:944–50.PubMedCrossRef Hsueh C, Chang YS, Tseng NM, Liao CT, Hsueh S, Chang JH, et al. Expression pattern and prognostic significance of claudins 1, 4, and 7 in nasopharyngeal carcinoma. Hum Pathol. 2010;41:944–50.PubMedCrossRef
43.
go back to reference Ohtani S, Terashima M, Satoh J, Soeta N, Saze Z, Kashimura S, et al. Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival. Gastric Cancer. 2009;12:43–51.PubMedCrossRef Ohtani S, Terashima M, Satoh J, Soeta N, Saze Z, Kashimura S, et al. Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival. Gastric Cancer. 2009;12:43–51.PubMedCrossRef
44.
go back to reference Michl P, Buchholz M, Rolke M, Kunsch S, Löhr M, McClane B, et al. Claudin-4: a new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin. Gastroenterology. 2001;121:678–84.PubMedCrossRef Michl P, Buchholz M, Rolke M, Kunsch S, Löhr M, McClane B, et al. Claudin-4: a new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin. Gastroenterology. 2001;121:678–84.PubMedCrossRef
45.
go back to reference Suzuki M, Kato-Nakano M, Kawamoto S, Furuya A, Abe Y, Misaka H, et al. Therapeutic antitumor efficacy of monoclonal antibody against Claudin-4 for pancreatic and ovarian cancers. Cancer Sci. 2009;100:1623–30.PubMedCrossRef Suzuki M, Kato-Nakano M, Kawamoto S, Furuya A, Abe Y, Misaka H, et al. Therapeutic antitumor efficacy of monoclonal antibody against Claudin-4 for pancreatic and ovarian cancers. Cancer Sci. 2009;100:1623–30.PubMedCrossRef
46.
go back to reference Kakutani H, Kondoh M, Saeki R, Fujii M, Watanabe Y, Mizuguchi H, et al. Claudin-4-targeting of diphtheria toxin fragment A using a C-terminal fragment of Clostridium perfringens enterotoxin. Eur J Pharm Biopharm. 2010;75:213–7.PubMedCrossRef Kakutani H, Kondoh M, Saeki R, Fujii M, Watanabe Y, Mizuguchi H, et al. Claudin-4-targeting of diphtheria toxin fragment A using a C-terminal fragment of Clostridium perfringens enterotoxin. Eur J Pharm Biopharm. 2010;75:213–7.PubMedCrossRef
47.
go back to reference Foss CA, Fox JJ, Feldmann G, Maitra A, Iacobuzio-Donohue C, Kern SE, et al. Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer. Mol Imaging. 2007;6:131–9.PubMed Foss CA, Fox JJ, Feldmann G, Maitra A, Iacobuzio-Donohue C, Kern SE, et al. Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer. Mol Imaging. 2007;6:131–9.PubMed
Metadata
Title
Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma
Authors
Kosuke Tsutsumi, MD, PhD
Norihiro Sato, MD, PhD
Reiko Tanabe, MD
Kazuhiro Mizumoto, MD, PhD
Katsuya Morimatsu, MD
Tadashi Kayashima, MD
Hayato Fujita, MD, PhD
Kenoki Ohuchida, MD, PhD
Takao Ohtsuka, MD, PhD
Shunichi Takahata, MD, PhD
Masafumi Nakamura, MD, PhD
Masao Tanaka, MD, PhD, FACS
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1970-2

Other articles of this Special Issue 3/2012

Annals of Surgical Oncology 3/2012 Go to the issue