Virchows Archiv

, Volume 451, Issue 3, pp 669–680 | Cite as

Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions

  • Fabio Facchetti
  • Silvia Lonardi
  • Francesca Gentili
  • Luisa Bercich
  • Marcella Falchetti
  • Regina Tardanico
  • Carla Baronchelli
  • Laura Lucini
  • Alessandro Santin
  • Bruno Murer
Original Article

Abstract

We evaluated the usefulness of the tight-junction associated protein Claudin 4 (CL-4) in the diagnosis of mesothelioma and mimickers, analyzing biopsies from 454 tumors, including 82 mesotheliomas, 336 carcinomas of different origin (278 primary, 58 metastatic to serosae), 36 nonepithelial spindle cell neoplasms, as well as 97 cytological samples from reactive effusions (12), mesothelioma (23) and metastatic carcinomas (62). CL-4 was consistently negative in normal and reactive mesothelium, as well as in all 82 mesotheliomas. In contrast, strong reactivity was found in 57/58 serosal metastasis, and in 245/278 primary carcinomas, with uppermost expression (150/153) in those most frequently involved in the differential with mesothelioma (lung, breast, gastrointestinal tract, pancreas, ovary, primary serous papillary carcinoma of peritoneum). On effusions, reactive and neoplastic mesothelial cells were regularly negative, while metastatic tumor cells stained positively in 60/62 (96.8%) cases. Among spindle cell neoplasms, only 2/9 biphasic synovial sarcomas and 4/4 follicular dendritic cell sarcomas stained positively. Results indicate that CL-4 reacts with the majority of epithelial neoplasms that often metastasize to serous membranes, representing a pancarcinoma marker with extremely high sensitivity and specificity. CL-4 may be considered a primary immunohistochemical reagent to rule out the diagnosis of mesothelioma.

Keywords

Claudin 4 Tight junctions Mesothelioma Carcinoma Follicular dendritic cells Immunohistochemistry 

References

  1. 1.
    Abutaily AS, Addis BJ, Roche WR (2002) Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 55:662–668PubMedCrossRefGoogle Scholar
  2. 2.
    Aerts JG, Delahaye M, van der Kwast TH, Davidson B, Hoogsteden HC, van Meerbeeck JP (2006) The high post-test probability of a cytological examination renders further investigations to establish a diagnosis of epithelial malignant pleural mesothelioma redundant. Diagn Cytopathol 34:523–527PubMedCrossRefGoogle Scholar
  3. 3.
    Agarwal R, D’Souza T, Morin PJ (2005) Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res 65:7378–7385PubMedCrossRefGoogle Scholar
  4. 4.
    Attanoos RL, Dojcinov SD, Webb R, Gibbs AR (2000) Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms. Histopathology 37:224–231PubMedCrossRefGoogle Scholar
  5. 5.
    Attanoos RL, Webb R, Dojcinov SD, Gibbs AR (2002) Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum. Histopathology 40:237–244PubMedCrossRefGoogle Scholar
  6. 6.
    Baker PM, Clement PB, Young RH (2005) Malignant peritoneal mesothelioma in women: a study of 75 cases with emphasis on their morphologic spectrum and differential diagnosis. Am J Clin Pathol 123:724–737PubMedCrossRefGoogle Scholar
  7. 7.
    Barnetson RJ, Burnett RA, Downie I, Harper CM, Roberts F (2006) Immunohistochemical analysis of peritoneal mesothelioma and primary and secondary serous carcinoma of the peritoneum: antibodies to estrogen and progesterone receptors are useful. Am J Clin Pathol 125:67–76PubMedCrossRefGoogle Scholar
  8. 8.
    Bassarova AV, Nesland JM, Davidson B (2006) D2–40 is not a specific marker for cells of mesothelial origin in serous effusions. Am J Surg Pathol 30:878–882PubMedCrossRefGoogle Scholar
  9. 9.
    Bignotti E, Tassi RA, Calza S, Ravaggi A, Romani C, Rossi E, Falchetti M, Odicino FE, Pecorelli S, Santin AD (2006) Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: identification of novel molecular biomarkers for early diagnosis and therapy. Gynecol Oncol 103:405–416PubMedCrossRefGoogle Scholar
  10. 10.
    Chan JKC (1997) Proliferative lesions of follicular dendritic cells: an overview, including a detailed account of follicular dendritic cell sarcoma, a neoplasm with many faces and uncommon etiologic associations. Adv Anat Pathol 4:387–411CrossRefGoogle Scholar
  11. 11.
    Cunningham SC, Kamangar F, Kim MP, Hammoud S, Haque R, Iacobuzio-Donahue CA, Maitra A, Ashfaq R, Hustinx S, Heitmiller RE, Choti MA, Lillemoe KD, Cameron JL, Yeo CJ, Schulick RD, Montgomery E (2006) Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions. Cancer Epidemiol Biomarkers Prev 15:281–287PubMedCrossRefGoogle Scholar
  12. 12.
    Davidson B, Zhang Z, Kleinberg L, Li M, Florenes VA, Wang TL, Shih Ie M (2006) Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from diffuse malignant peritoneal mesothelioma. Clin Cancer Res 12:5944–5950PubMedCrossRefGoogle Scholar
  13. 13.
    de Oliveira SS, de Oliveira IM, De Souza W, Morgado-Diaz JA (2005) Claudins upregulation in human colorectal cancer. FEBS Lett 579:6179–6185PubMedCrossRefGoogle Scholar
  14. 14.
    Haratake J, Hashimoto H (1995) An immunohistochemical analysis of 13 cases with combined hepatocellular and cholangiocellular carcinoma. Liver 15:9–15PubMedGoogle Scholar
  15. 15.
    Hewitt KJ, Agarwal R, Morin PJ (2006) The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer 6:186PubMedCrossRefGoogle Scholar
  16. 16.
    Honda H, Pazin MJ, Ji H, Wernyj RP, Morin PJ (2006) Crucial roles of Sp1 and epigenetic modifications in the regulation of the CLDN4 promoter in ovarian cancer cells. J Biol Chem 281:21433–21444PubMedCrossRefGoogle Scholar
  17. 17.
    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 60:6281–6287PubMedGoogle Scholar
  18. 18.
    Katahira J, Sugiyama H, Inoue N, Horiguchi Y, Matsuda M, Sugimoto N (1997) Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. J Biol Chem 272:26652–26658PubMedCrossRefGoogle Scholar
  19. 19.
    King JE, Thatcher N, Pickering CA, Hasleton PS (2006) Sensitivity and specificity of immunohistochemical markers used in the diagnosis of epithelioid mesothelioma: a detailed systematic analysis using published data. Histopathology 48:223–232PubMedCrossRefGoogle Scholar
  20. 20.
    Ko EC, Jhala NC, Shultz JJ, Chhieng DC (2001) Use of a panel of markers in the differential diagnosis of adenocarcinoma and reactive mesothelial cells in fluid cytology. Am J Clin Pathol 116:709–715PubMedCrossRefGoogle Scholar
  21. 21.
    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 164:1627–1633PubMedGoogle Scholar
  22. 22.
    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 22:2021–2033PubMedCrossRefGoogle Scholar
  23. 23.
    Le Moellic C, Boulkroun S, Gonzalez-Nunez D, Dublineau I, Cluzeaud F, Fay M, Blot-Chabaud M, Farman N (2005) Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells. Am J Physiol Cell Physiol 289:C1513–1521PubMedCrossRefGoogle Scholar
  24. 24.
    Lin BT, Colby T, Gown AM, Hammar SP, Mertens RB, Churg A, Battifora H (1996) Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases. Am J Surg Pathol 20:1431–1439PubMedCrossRefGoogle Scholar
  25. 25.
    Lodi C, Szabo E, Holczbauer A, Batmunkh E, Szijarto A, Kupcsulik P, Kovalszky I, Paku S, Illyes G, Kiss A, Schaff Z (2006) Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas. Mod Pathol 19:460–469PubMedCrossRefGoogle Scholar
  26. 26.
    Long H, Crean CD, Lee WH, Cummings OW, Gabig TG (2001) Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res 61:7878–7881PubMedGoogle Scholar
  27. 27.
    Loy TS, Nashelsky MB (1993) Reactivity of B72.3 with adenocarcinomas. An immunohistochemical study of 476 cases. Cancer 72:2495–2498PubMedCrossRefGoogle Scholar
  28. 28.
    Lozano MD, Panizo A, Toledo GR, Sola JJ, Pardo-Mindan J (2001) Immunocytochemistry in the differential diagnosis of serous effusions: a comparative evaluation of eight monoclonal antibodies in Papanicolaou stained smears. Cancer 93:68–72PubMedCrossRefGoogle Scholar
  29. 29.
    Lucas DR, Pass HI, Madan SK, Adsay NV, Wali A, Tabaczka P, Lonardo F (2003) Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study. Histopathology 42:270–279PubMedCrossRefGoogle Scholar
  30. 30.
    Ma CK, Zarbo RJ, Frierson HF Jr, Lee MW (1993) Comparative immunohistochemical study of primary and metastatic carcinomas of the liver. Am J Clin Pathol 99:551–557PubMedGoogle Scholar
  31. 31.
    Mark EJ, Kradin RL (2006) Pathological recognition of diffuse malignant mesothelioma of the pleura: the significance of the historical perspective as regards this signal tumor. Semin Diagn Pathol 23:25–34PubMedCrossRefGoogle Scholar
  32. 32.
    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 121:678–684PubMedCrossRefGoogle Scholar
  33. 33.
    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 63:6265–6271PubMedGoogle Scholar
  34. 34.
    Mitic LL, Anderson JM (1998) Molecular architecture of tight junctions. Annu Rev Physiol 60:121–142PubMedCrossRefGoogle Scholar
  35. 35.
    Montgomery E, Mamelak AJ, Gibson M, Maitra A, Sheikh S, Amr SS, Yang S, Brock M, Forastiere A, Zhang S, Murphy KM, Berg KD (2006) Overexpression of claudin proteins in esophageal adenocarcinoma and its precursor lesions. Appl Immunohistochem Mol Morphol 14:24–30PubMedCrossRefGoogle Scholar
  36. 36.
    Morin PJ (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65:9603–9606PubMedCrossRefGoogle Scholar
  37. 37.
    Morita K, Tsukita S, Miyachi Y (2004) Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen’s disease. Br J Dermatol 151:328–334PubMedCrossRefGoogle Scholar
  38. 38.
    Morita K, Furuse M, Fujimoto K, Tsukita S (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci USA 96:511–516PubMedCrossRefGoogle Scholar
  39. 39.
    Morrison C, Marsh W Jr, Frankel WL (2002) A comparison of CD10 to pCEA, MOC-31, and hepatocyte for the distinction of malignant tumors in the liver. Mod Pathol 15:1279–1287PubMedCrossRefGoogle Scholar
  40. 40.
    Nagaraja GM, Othman M, Fox BP, Alsaber R, Pellegrino CM, Zeng Y, Khanna R, Tamburini P, Swaroop A, Kandpal RP (2006) Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics. Oncogene 25:2328–2338PubMedCrossRefGoogle Scholar
  41. 41.
    Niemann TH, Hughes JH, De Young BR (1999) MOC-31 aids in the differentiation of metastatic adenocarcinoma from hepatocellular carcinoma. Cancer 87:295–298PubMedCrossRefGoogle Scholar
  42. 42.
    Ordonez NG (2002) Immunohistochemical diagnosis of epithelioid mesotheliomas: a critical review of old markers, new markers. Hum Pathol 33:953–967PubMedCrossRefGoogle Scholar
  43. 43.
    Ordonez NG (2003) The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol 27:1031–1051PubMedCrossRefGoogle Scholar
  44. 44.
    Ordonez NG (2004) The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study. Hum Pathol 35:697–710PubMedCrossRefGoogle Scholar
  45. 45.
    Ordonez NG (2005) Value of estrogen and progesterone receptor immunostaining in distinguishing between peritoneal mesotheliomas and serous carcinomas. Hum Pathol 36:1163–1167PubMedCrossRefGoogle Scholar
  46. 46.
    Ordonez NG (2005) Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med 129:1407–1414PubMedGoogle Scholar
  47. 47.
    Ordonez NG (2006) Value of immunohistochemistry in distinguishing peritoneal mesothelioma from serous carcinoma of the ovary and peritoneum: a review and update. Adv Anat Pathol 13:16–25PubMedCrossRefGoogle Scholar
  48. 48.
    Ordonez NG (2006) The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study. Mod Pathol 19:417–428PubMedCrossRefGoogle Scholar
  49. 49.
    Ordonez NG (2006) The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study. Mod Pathol 19:34–48PubMedCrossRefGoogle Scholar
  50. 50.
    Ordonez NG (2007) What are the current best immunohistochemical markers for the diagnosis of epithelioid mesothelioma? A review and update. Hum Pathol 38:1–16PubMedCrossRefGoogle Scholar
  51. 51.
    Pan CC, Chen PC, Ho DM (2004) The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases. Histopathology 45:452–459PubMedCrossRefGoogle Scholar
  52. 52.
    Pereira TC, Saad RS, Liu Y, Silverman JF (2006) The diagnosis of malignancy in effusion cytology: a pattern recognition approach. Adv Anat Pathol 13:174–184PubMedCrossRefGoogle Scholar
  53. 53.
    Politi E, Kandaraki C, Apostolopoulou C, Kyritsi T, Koutselini H (2005) Immunocytochemical panel for distinguishing between carcinoma and reactive mesothelial cells in body cavity fluids. Diagn Cytopathol 32:151–155PubMedCrossRefGoogle Scholar
  54. 54.
    Porcell AI, De Young BR, Proca DM, Frankel WL (2000) Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. Mod Pathol 13:773–778PubMedCrossRefGoogle Scholar
  55. 55.
    Porta C, Ardizzoni A, Gaudino G, Maio M, Mutti L, Pinto C, Porru S, Puntoni R, Tassi G, Tognon M (2005) Malignant mesothelioma in 2004: How advanced technology and new drugs are changing the perspectives of mesothelioma patients. Highlights from the VIIth Meeting of the International Mesothelioma Interest Group. Med Lav 96:360–369PubMedGoogle Scholar
  56. 56.
    Rangel LB, Agarwal R, D’Souza T, Pizer ES, Alo PL, Lancaster WD, Gregoire L, Schwartz DR, Cho KR, Morin PJ (2003) Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas. Clin Cancer Res 9:2567–2575PubMedGoogle Scholar
  57. 57.
    Resnick MB, Gavilanez M, Newton E, Konkin T, Bhattacharya B, Britt DE, Sabo E, Moss SF (2005) Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation. Hum Pathol 36:886–892PubMedCrossRefGoogle Scholar
  58. 58.
    Riera JR, Astengo-Osuna C, Longmate JA, Battifora H (1997) The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat-induced epitope retrieval. Am J Surg Pathol 21:1409–1419PubMedCrossRefGoogle Scholar
  59. 59.
    Roberts F, Harper CM, Downie I, Burnett RA (2001) Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies. Am J Clin Pathol 116:253–262PubMedCrossRefGoogle Scholar
  60. 60.
    Sanada Y, Oue N, Mitani Y, Yoshida K, Nakayama H, Yasui W (2006) Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype. J Pathol 208:633–642PubMedCrossRefGoogle Scholar
  61. 61.
    Santin AD, Cane S, Bellone S, Palmieri M, Siegel ER, Thomas M, Roman JJ, Burnett A, Cannon MJ, Pecorelli S (2005) Treatment of chemotherapy-resistant human ovarian cancer xenografts in C.B-17/SCID mice by intraperitoneal administration of Clostridium perfringens enterotoxin. Cancer Res 65:4334–4342PubMedCrossRefGoogle Scholar
  62. 62.
    Santin AD, Zhan F, Cane S, Bellone S, Palmieri M, Thomas M, Burnett A, Roman JJ, Cannon MJ, Shaughnessy J Jr, Pecorelli S (2005) Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. Br J Cancer 92:1561–1573PubMedCrossRefGoogle Scholar
  63. 63.
    Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Bignotti E, Anfossi S, Gokden M, Dunn D, Roman JJ, O’Brien TJ, Tian E, Cannon MJ, Shaughnessy J Jr, Pecorelli S (2004) Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy. Int J Cancer 112:14–25PubMedCrossRefGoogle Scholar
  64. 64.
    Sato N, Fukushima N, Maitra A, Iacobuzio-Donahue CA, van Heek NT, Cameron JL, Yeo CJ, Hruban RH, Goggins M (2004) Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas. Am J Pathol 164:903–914PubMedGoogle Scholar
  65. 65.
    Simsir A, Fetsch P, Abati A (2001) Calretinin immunostaining in benign and malignant pleural effusions. Diagn Cytopathol 24:149–152PubMedCrossRefGoogle Scholar
  66. 66.
    Simsir A, Fetsch P, Mehta D, Zakowski M, Abati A (1999) E-cadherin, N-cadherin, and calretinin in pleural effusions: the good, the bad, the worthless. Diagn Cytopathol 20:125–130PubMedCrossRefGoogle Scholar
  67. 67.
    Soini Y (2004) Claudins 2, 3, 4, and 5 in Paget's disease and breast carcinoma. Hum Pathol 35:1531–1536PubMedCrossRefGoogle Scholar
  68. 68.
    Soini Y (2005) Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology 46:551–560PubMedCrossRefGoogle Scholar
  69. 69.
    Soini Y, Talvensaari-Mattila A (2006) Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types. Int J Gynecol Pathol 25:330–335PubMedCrossRefGoogle Scholar
  70. 70.
    Soini Y, Tommola S, Helin H, Martikainen P (2006) Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch 448:52–58PubMedCrossRefGoogle Scholar
  71. 71.
    Soini Y, Kinnula V, Kahlos K, Paakko P (2006) Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura. J Clin Pathol 59:250–254PubMedCrossRefGoogle Scholar
  72. 72.
    Sun X, Chang KC, Abruzzo LV, Lai R, Younes A, Jones D (2003) Epidermal growth factor receptor expression in follicular dendritic cells: a shared feature of follicular dendritic cell sarcoma and Castleman’s disease. Hum Pathol 34:835–840PubMedCrossRefGoogle Scholar
  73. 73.
    Suster S, Moran CA (2006) Applications and limitations of immunohistochemistry in the diagnosis of malignant mesothelioma. Adv Anat Pathol 13:316–329PubMedCrossRefGoogle Scholar
  74. 74.
    Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) Tumors of the lung, pleura, thymus and hearth. Pathology and genetics. IARC, LyonGoogle Scholar
  75. 75.
    Wang L, Vuolo M, Suhrland MJ, Schlesinger K (2006) HepPar1, MOC-31, pCEA, mCEA and CD10 for distinguishing hepatocellular carcinoma vs. metastatic adenocarcinoma in liver fine needle aspirates. Acta Cytol 50:257–262PubMedGoogle Scholar
  76. 76.
    Yaziji H, Battifora H, Barry TS, Hwang HC, Bacchi CE, McIntosh MW, Kussick SJ, Gown AM (2006) Evaluation of 12 antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma: identification of a three-antibody immunohistochemical panel with maximal sensitivity and specificity. Mod Pathol 19:514–523PubMedCrossRefGoogle Scholar
  77. 77.
    Zhu Y, Brannstrom M, Janson PO, Sundfeldt K (2006) Differences in expression patterns of the tight junction proteins,claudin 1, 3, 4 and 5, in human ovarian surface epithelium as compared to epithelia in inclusion cysts and epithelial ovarian tumours. Int J Cancer 118:1884–1891PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Fabio Facchetti
    • 1
  • Silvia Lonardi
    • 1
  • Francesca Gentili
    • 1
  • Luisa Bercich
    • 1
  • Marcella Falchetti
    • 1
  • Regina Tardanico
    • 1
  • Carla Baronchelli
    • 1
  • Laura Lucini
    • 1
  • Alessandro Santin
    • 2
  • Bruno Murer
    • 3
  1. 1.Department of Pathology IUniversity of BresciaBresciaItaly
  2. 2.Department of Obstetrics and GynaecologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Department of PathologyMestre HospitalMestreItaly

Personalised recommendations