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

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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.

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Abbreviations

CLDN:

Claudin (gene)

CPE:

Clostridium perfringens enterotoxin

EMT:

Epithelial–mesenchymal transition

MET:

Mesenchymal–epithelial transition

IDC:

Invasive ductal carcinoma

ILC:

Invasive lobular carcinoma

LNM:

Lymph node metastasis

PCR:

Polymerase chain reaction

TJ:

Tight junction

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Acknowledgments

The authors thank the kind help of Azumah Francisné, Pekár Zoltánné and Samodai Erika in the preparation of slides and immunohistochemistry. The study was supported by the following grants: ETT-049/2006, OTKA-49559/2005, Rosztóczy Foundation.

Conflict of interests

The authors have no interests to disclose.

Author information

Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, Ulloi ut 93, Budapest, 1091, Hungary

    A. M. Szasz, A. M. Tokes, L. Lukacs, Zs. Nemeth, L. Madaras & J. Kulka

  2. Sackler Institute, New York University, New York, USA

    M. Micsinai

  3. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    T. Krenacs

  4. Department of Pathology and Forensic Veterinary Medicine, Faculty of Veterinary Medicine, Szent Istvan University, Budapest, Hungary

    Cs. Jakab

  5. Department of Surgery and Vascular Surgery, Uzsoki Memorial Hospital, Budapest, Hungary

    Zs. Baranyai & K. Dede

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  1. A. M. Szasz
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  11. J. Kulka
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Corresponding author

Correspondence to J. Kulka.

Additional information

Attila Marcell Szasz and Anna-Maria Tokes are the authors contributed equally to the work.

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Szasz, A.M., Tokes, A.M., Micsinai, M. et al. Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis. Clin Exp Metastasis 28, 55–63 (2011). https://doi.org/10.1007/s10585-010-9357-5

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