Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 1/2011

01-01-2011 | Research Paper

Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis

Authors: A. M. Szasz, A. M. Tokes, M. Micsinai, T. Krenacs, Cs. Jakab, L. Lukacs, Zs. Nemeth, Zs. Baranyai, K. Dede, L. Madaras, J. Kulka

Published in: Clinical & Experimental Metastasis | Issue 1/2011

Login to get access

Abstract

Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.
Appendix
Available only for authorised users
Literature
1.
Paul S, Dey A (2008) Wnt signaling and cancer development: therapeutic implication. Neoplasma 55(3):165–176PubMed
2.
3.
Saldanha G, Ghura V, Potter L et al (2004) Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation. Br J Dermatol 151(1):157–164CrossRefPubMed
4.
Hashizume R, Koizumi H, Ihara A et al (1996) Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin. Histopathology 29(2):139–146CrossRefPubMed
5.
De Leeuw WJ, Berx G, Vos CB et al (1997) Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol 183(4):404–411CrossRefPubMed
6.
Karayiannakis AJ, Nakopoulou L, Gakiopoulou H et al (2001) Expression patterns of beta-catenin in in situ and invasive breast cancer. Eur J Surg Oncol 27(1):31–36CrossRefPubMed
7.
Mastracci TL, Tjan S, Bane AL et al (2005) E-cadherin alterations in atypical lobular hyperplasia and lobular carcinoma in situ of the breast. Mod Pathol 18(6):741–751CrossRefPubMed
8.
Kuroda H, Tamaru J, Takeuchi I et al (2006) Expression of E-cadherin, alpha-catenin, and beta-catenin in tubulolobular carcinoma of the breast. Virchows Arch 448(4):500–505CrossRefPubMed
9.
Furuse M, Fujita K, Hiiragi T et al (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141(7):1539–1550CrossRefPubMed
10.
Hewitt KJ, Agarwal R, Morin PJ (2006) The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer 6:186CrossRefPubMed
11.
Kulka J, Tokes AM (2005) Claudin expression in breast tumors. Hum Pathol 36(7):859 (author reply 60)CrossRefPubMed
12.
Morohashi S, Kusumi T, Sato F et al (2007) Decreased expression of claudin-1 correlates with recurrence status in breast cancer. Int J Mol Med 20(2):139–143PubMed
13.
Kim TH, Huh JH, Lee S et al (2008) Down-regulation of claudin-2 in breast carcinomas is associated with advanced disease. Histopathology 53(1):48–55CrossRefPubMed
14.
Tokes AM, Kulka J, Paku S et al (2005) Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res 7(2):R296–R305CrossRefPubMed
15.
Blackman B, Russell T, Nordeen SK et al (2005) Claudin 7 expression and localization in the normal murine mammary gland and murine mammary tumors. Breast Cancer Res 7(2):R248–R255CrossRefPubMed
16.
Kominsky SL, Argani P, Korz D et al (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(13):2021–2033CrossRefPubMed
17.
Sauer T, Pedersen MK, Ebeltoft K et al (2005) Reduced expression of claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease. Cytopathology 16(4):193–198CrossRefPubMed
18.
Blanchard AA, Skliris GP, Watson PH et al (2009) Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype. Virchows Arch 454(6):647–656
19.
Kulka J, Szasz AM, Nemeth Z et al (2009) Expression of tight junction protein claudin-4 in basal-like breast carcinomas. Pathol Oncol Res 15(1):59–64CrossRefPubMed
20.
Lanigan F, McKiernan E, Brennan DJ et al (2009) Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer. Int J Cancer 124(9):2088–2097CrossRefPubMed
21.
Soini Y (2005) Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology 46(5):551–560CrossRefPubMed
22.
Park D, Karesen R, Axcrona U et al (2007) Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. APMIS 115(1):52–65CrossRefPubMed
23.
Herschkowitz JI, Simin K, Weigman VJ et al (2007) Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 8(5):R76CrossRefPubMed
24.
Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K et al (2009) Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 69(10):4116–4124CrossRefPubMed
25.
Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMed
26.
Kulka J, Szasz A, Nemeth Z et al (2009) Expression of tight junction protein claudin-4 in basal-like breast carcinomas. Pathol Oncol Res 15(1):59–64
27.
Eckel-Passow J, Lohse C, Sheinin Y et al (2010) Tissue microarrays: one size does not fit all. Diagn Pathol 5(1):48CrossRefPubMed
28.
Avninder S, Ylaya K, Hewitt S (2008) Tissue microarray: a simple technology that has revolutionized research in pathology. J Postgrad Med 54(2):158–162
29.
Drury S, Salter J, Baehner FL et al (2010) Feasibility of using tissue microarray cores of paraffin-embedded breast cancer tissue for measurement of gene expression: a proof-of-concept study. J Clin Pathol 63(6):513–517CrossRefPubMed
30.
Soini Y (2004) Claudins 2, 3, 4, and 5 in Paget’s disease and breast carcinoma. Hum Pathol 35(12):1531–1536CrossRefPubMed
31.
Chao YC, Pan SH, Yang SC et al (2009) Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma. Am J Respir Crit Care Med 179(2):123–133CrossRefPubMed
32.
Fritzsche FR, Oelrich B, Johannsen M et al (2008) Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas. Clin Cancer Res 14(21):7035–7042CrossRefPubMed
33.
Higashi Y, Suzuki S, Sakaguchi T et al (2007) Loss of claudin-1 expression correlates with malignancy of hepatocellular carcinoma. J Surg Res 139(1):68–76CrossRefPubMed
34.
Lechpammer M, Resnick MB, Sabo E et al (2008) The diagnostic and prognostic utility of claudin expression in renal cell neoplasms. Mod Pathol 21(11):1320–1329CrossRefPubMed
35.
Resnick MB, Konkin T, Routhier J et al (2005) Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol 18(4):511–518CrossRefPubMed
36.
Lanigan F, McKiernan E, Brennan DJ et al (2008) Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer. Int J Cancer 124:2088–2097
37.
Krajewska M, Olson AH, Mercola D et al (2007) Claudin-1 immunohistochemistry for distinguishing malignant from benign epithelial lesions of prostate. Prostate 67(9):907–910CrossRefPubMed
38.
Landers KA, Samaratunga H, Teng L et al (2008) Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer. Br J Cancer 99(3):491–501CrossRefPubMed
39.
Wang M, Xue L, Cao Q et al (2009) Expression of Notch1, Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma. Neoplasma 56(6):533–541CrossRefPubMed
40.
Orsulic S, Huber O, Aberle H et al (1999) E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci 112(Pt 8):1237–1245PubMed
41.
Birchmeier C, Birchmeier W, Brand-Saberi B (1996) Epithelial–mesenchymal transitions in cancer progression. Acta Anat 156(3):217–226CrossRefPubMed
42.
Yang J, Weinberg RA (2008) Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14(6):818–829CrossRefPubMed
43.
Hugo H, Ackland ML, Blick T et al (2007) Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 213(2):374–383CrossRefPubMed
44.
Huber MA, Kraut N, Beug H (2005) Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol 17(5):548–558CrossRefPubMed
45.
Thiery JP, Acloque H, Huang RY et al (2009) Epithelial–mesenchymal transitions in development and disease. Cell 139(5):871–890CrossRefPubMed
46.
Onder TT, Gupta PB, Mani SA et al (2008) Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 68(10):3645–3654CrossRefPubMed
47.
Creighton CJ, Chang JC, Rosen JM Epithelial–mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. J Mammary Gland Biol Neoplasia
48.
Perou C (2009) Overview of gene expression profiling and novel translational technologies in breast cancer. Cancer Res 69(24_Meeting Abstracts):ES3-1
49.
Szasz AM, Micsinai M, Tokes A et al (2009) Proteomic profiling of breast carcinomas based on claudin expression pattern. Cancer Res 69(24_Meeting Abstracts):6123
50.
51.
Yoshida R, Kimura N, Harada Y et al (2001) The loss of E-cadherin, alpha- and beta-catenin expression is associated with metastasis and poor prognosis in invasive breast cancer. Int J Oncol 18(3):513–520PubMed
52.
Bukholm IK, Nesland JM, Karesen R et al (1998) E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol 185(3):262–266CrossRefPubMed
53.
Cowin P, Rowlands TM, Hatsell SJ (2005) Cadherins and catenins in breast cancer. Curr Opin Cell Biol 17(5):499–508CrossRefPubMed
54.
Goyal A, Martin TA, Mansel RE et al (2008) Real time PCR analyses of expression of E-cadherin, alpha-, beta- and gamma-catenin in human breast cancer for predicting clinical outcome. World J Surg Oncol 6:56CrossRefPubMed
55.
Gyorffy H, Holczbauer A, Nagy P et al (2005) Claudin expression in Barrett’s esophagus and adenocarcinoma. Virchows Arch 447(6):961–968CrossRefPubMed
56.
Lodi C, Szabo E, Holczbauer A et al (2006) Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas. Mod Pathol 19(3):460–469CrossRefPubMed
57.
Szabo I, Kiss A, Schaff Z et al (2009) Claudins as diagnostic and prognostic markers in gynecological cancer. Histol Histopathol 24(12):1607–1615PubMed
Metadata
Title
Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis
Authors
A. M. Szasz
A. M. Tokes
M. Micsinai
T. Krenacs
Cs. Jakab
L. Lukacs
Zs. Nemeth
Zs. Baranyai
K. Dede
L. Madaras
J. Kulka
Publication date
01-01-2011
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 1/2011
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-010-9357-5

Other articles of this Issue 1/2011

Clinical & Experimental Metastasis 1/2011 Go to the issue

Research Paper

Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis

Research Paper

Platelet adhesion and fusion to endothelial cell facilitate the metastasis of tumor cell in hypoxia-reoxygenation condition

Research Paper

Endoglin suppresses human prostate cancer metastasis

Research Paper

High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

Research Paper

Differential expression of tartrate-resistant acid phosphatase isoforms 5a and 5b by tumor and stromal cells in human metastatic bone disease

Research Paper

Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits