Skip to main content
Erschienen in: Virchows Archiv 1/2006

01.01.2006 | Original Article

Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype

verfasst von: Y. Soini, S. Tommola, H. Helin, P. Martikainen

Erschienen in: Virchows Archiv | Ausgabe 1/2006

Einloggen, um Zugang zu erhalten

Abstract

In this study expression of claudins 1, 3, 4 and 5 were studied in 118 cases of gastric carcinoma and compared with proliferation, apoptosis and E-cadherin expression. Expression of all these claudins could be seen in gastric carcinoma, most prominently for claudin 4, and least expression was found for claudin 5. All claudins showed significantly more expression in gastric carcinomas of intestinal type. Their expression was significantly associated with each other. Expression of claudins 4 and 5 was associated with E-cadherin. Strong expression of claudin 5 was associated with higher cell proliferation and apoptosis. Claudin 3 expression had an association with a better prognosis of the patients, especially in the intestinal type. The results show that expression of claudins 1, 3, 4 and 5 is lower in diffuse-type gastric carcinomas. Possibly they play a role in determining the diffuse phenotype and loose cohesion of cells in diffuse type of gastric carcinoma in a similar manner as E-cadherin. The loss of their expression does not clearly associate with poorer prognosis of the patients, except for claudin 3, where strong expression was associated with a better outcome of the patients, a feature especially related to intestinal-type tumours.
Literatur
1.
Zurück zum Zitat Folpe AL, Billings SD, McKenney JK, Walsh SV, Nusrat A, Weiss SW (2002) Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. Am J Surg Pathol 26:1620–1626PubMedCrossRef Folpe AL, Billings SD, McKenney JK, Walsh SV, Nusrat A, Weiss SW (2002) Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. Am J Surg Pathol 26:1620–1626PubMedCrossRef
2.
Zurück zum Zitat Gumbiner B, Stevenson B, Grimaldi A (1988) The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol 107:1575–1587PubMedCrossRef Gumbiner B, Stevenson B, Grimaldi A (1988) The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol 107:1575–1587PubMedCrossRef
3.
Zurück zum Zitat Hamilton SR, Aaltonen LA (2000) Tumours of the digestive system. Pathology and genetics. World Health Organization classification of tumours. IARC Press, Lyon, France Hamilton SR, Aaltonen LA (2000) Tumours of the digestive system. Pathology and genetics. World Health Organization classification of tumours. IARC Press, Lyon, France
4.
Zurück zum Zitat Hough CD, Sherman-Baust CA, Pizer ES, Montz FJ, Im DD, Rosenshein NB, Cho KR, Riggins GJ, Morin PJ (2000) Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res 60:6281–6287PubMed Hough CD, Sherman-Baust CA, Pizer ES, Montz FJ, Im DD, Rosenshein NB, Cho KR, Riggins GJ, Morin PJ (2000) Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res 60:6281–6287PubMed
5.
Zurück zum Zitat Kiuchi-Saishin Y, Gotoh S, Furuse M, Takasuga A, Tano Y, Tsukita S (2002) Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments. J Am Soc Nephrol 13:875–886PubMed Kiuchi-Saishin Y, Gotoh S, Furuse M, Takasuga A, Tano Y, Tsukita S (2002) Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments. J Am Soc Nephrol 13:875–886PubMed
6.
Zurück zum Zitat Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S (2003) Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene 22:2021–2033PubMedCrossRef Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S (2003) Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene 22:2021–2033PubMedCrossRef
7.
Zurück zum Zitat Kominsky SL, Vali M, Korz D, Gabig TG, Weitzman SA, Argani P, Sukumar S (2004) Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am J Pathol 164:1627–1633PubMed Kominsky SL, Vali M, Korz D, Gabig TG, Weitzman SA, Argani P, Sukumar S (2004) Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am J Pathol 164:1627–1633PubMed
8.
Zurück zum Zitat Lauren T (1965) The two histological main types of gastric carcinoma. Acta Pathol Microbiol Scand 64:34 Lauren T (1965) The two histological main types of gastric carcinoma. Acta Pathol Microbiol Scand 64:34
9.
Zurück zum Zitat Long H, Crean CD, Lee W-H, Cummings OW, Gabig TG (2001) Expression of clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res 61:7878–7881PubMed Long H, Crean CD, Lee W-H, Cummings OW, Gabig TG (2001) Expression of clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res 61:7878–7881PubMed
10.
Zurück zum Zitat Machado JC, Carneiro F, Beck S, Rossi S, Lopes J, Taveira GA (1998) E-cadherin expression is correlated with the isolated cell/diffuse histotype and with the features of biological aggressiveness of gastric carcinoma. Int J Surg Pathol 6:135–144CrossRef Machado JC, Carneiro F, Beck S, Rossi S, Lopes J, Taveira GA (1998) E-cadherin expression is correlated with the isolated cell/diffuse histotype and with the features of biological aggressiveness of gastric carcinoma. Int J Surg Pathol 6:135–144CrossRef
11.
Zurück zum Zitat Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I (1993) E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690–1695PubMed Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I (1993) E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690–1695PubMed
12.
Zurück zum Zitat Michl P, Barth C, Buchholz M, Lerch MM, Rolke M, Holzmann KH, Menke A, Fensterer H, Giehl K, Lohr M, Leder G, Iwamura T, Adler G, Gress TM (2003) Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res 63:6265–6271PubMed Michl P, Barth C, Buchholz M, Lerch MM, Rolke M, Holzmann KH, Menke A, Fensterer H, Giehl K, Lohr M, Leder G, Iwamura T, Adler G, Gress TM (2003) Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res 63:6265–6271PubMed
13.
Zurück zum Zitat Michl P, Buchholz M, Rolke M, Kunsch S, Lohr M, McClane B, Tsukita S, Leder G, Adler G, Gress TM (2001) Claudin 4: a new target for pancreatic cancer treatment using clostridium perfringens enterotoxin. Gastroenterology 121:678–684PubMedCrossRef Michl P, Buchholz M, Rolke M, Kunsch S, Lohr M, McClane B, Tsukita S, Leder G, Adler G, Gress TM (2001) Claudin 4: a new target for pancreatic cancer treatment using clostridium perfringens enterotoxin. Gastroenterology 121:678–684PubMedCrossRef
14.
Zurück zum Zitat Mitic LL, van Itallie CM, Anderson JM (2000) Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lesions from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol 279:G250–G254PubMed Mitic LL, van Itallie CM, Anderson JM (2000) Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lesions from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol 279:G250–G254PubMed
15.
Zurück zum Zitat Rahner C, Mitic LL, Anderson JM (2001) Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology 120:411–422PubMedCrossRef Rahner C, Mitic LL, Anderson JM (2001) Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology 120:411–422PubMedCrossRef
16.
Zurück zum Zitat Reyes JL, Lamas M, Martin D, del Carmen Namorado M, Islas S, Luna J, Tauc M, Gonzalez-Mariscal L (2002) The renal segmental distribution of claudins changes with development. Kidney Int 62:476–487PubMedCrossRef Reyes JL, Lamas M, Martin D, del Carmen Namorado M, Islas S, Luna J, Tauc M, Gonzalez-Mariscal L (2002) The renal segmental distribution of claudins changes with development. Kidney Int 62:476–487PubMedCrossRef
17.
Zurück zum Zitat Sanford JL, Edwards JD, Mays TA, Gong B, Merriam AP, Rafael-Fortney JA (2005) Claudin-5 localizes to the lateral membranes of cardiomyocytes and is altered in utrophin/dystrophin-deficient cardiomyopathic mice. J Mol Cell Cardiol 38:323–332PubMedCrossRef Sanford JL, Edwards JD, Mays TA, Gong B, Merriam AP, Rafael-Fortney JA (2005) Claudin-5 localizes to the lateral membranes of cardiomyocytes and is altered in utrophin/dystrophin-deficient cardiomyopathic mice. J Mol Cell Cardiol 38:323–332PubMedCrossRef
18.
Zurück zum Zitat Sobin LH, Wittekind CH (2002) TNM classification of malignant tumours. International Union Against Cancer (UICC), 6th edn. Wiley-Liss, New York Sobin LH, Wittekind CH (2002) TNM classification of malignant tumours. International Union Against Cancer (UICC), 6th edn. Wiley-Liss, New York
19.
Zurück zum Zitat Soini Y (2004) Claudins 2, 3, 4 and 5 in Paget's disease and breast carcinoma. Hum Pathol 35:1531–1536PubMedCrossRef Soini Y (2004) Claudins 2, 3, 4 and 5 in Paget's disease and breast carcinoma. Hum Pathol 35:1531–1536PubMedCrossRef
20.
Zurück zum Zitat Terris B, Blaveri E, Crnogorac-Jurcevic T, Jones M, Missiaglia E, Ruszniewski P, Sauvanet A, Lemoine NR (2002) Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas. Am J Pathol 160:1745–1754PubMed Terris B, Blaveri E, Crnogorac-Jurcevic T, Jones M, Missiaglia E, Ruszniewski P, Sauvanet A, Lemoine NR (2002) Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas. Am J Pathol 160:1745–1754PubMed
21.
Zurück zum Zitat Tokes AM, Kulka J, Paku S, Szik A, Paska C, Novak PK, Szilak L, Kiss A, Bögl K, Schaff Z (2005) Claudin 1, 3, and 4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res 7:R295–R305CrossRef Tokes AM, Kulka J, Paku S, Szik A, Paska C, Novak PK, Szilak L, Kiss A, Bögl K, Schaff Z (2005) Claudin 1, 3, and 4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res 7:R295–R305CrossRef
22.
Zurück zum Zitat Tsukita S, Furuse M (2000) Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol 149:13–16PubMedCrossRef Tsukita S, Furuse M (2000) Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol 149:13–16PubMedCrossRef
23.
Zurück zum Zitat Tsukita S, Furuse M (2002) Claudin-based barrier in simple and stratified cellular sheets. Curr Opin Cell Biol 14:531–536PubMedCrossRef Tsukita S, Furuse M (2002) Claudin-based barrier in simple and stratified cellular sheets. Curr Opin Cell Biol 14:531–536PubMedCrossRef
24.
25.
Zurück zum Zitat Wheelock MJ, Jensen PJ (1992) Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin. J Cell Biol 117:415–425PubMedCrossRef Wheelock MJ, Jensen PJ (1992) Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin. J Cell Biol 117:415–425PubMedCrossRef
Metadaten
Titel
Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype
verfasst von
Y. Soini
S. Tommola
H. Helin
P. Martikainen
Publikationsdatum
01.01.2006
Verlag
Springer-Verlag
Erschienen in
Virchows Archiv / Ausgabe 1/2006
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-005-0011-6

Weitere Artikel der Ausgabe 1/2006

Virchows Archiv 1/2006 Zur Ausgabe

Acknowledgement to Referees

Acknowledgment

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …

Personalisierte Medizin in der Onkologie

Aufgrund des erheblichen technologischen Fortschritts in der molekularen und genetischen Diagnostik sowie zunehmender Erkenntnisse über die molekulare Pathogenese von Krankheiten hat in den letzten zwei Jahrzehnten ein grundlegender …