University of Oulu

Jääskeläinen, A., Soini, Y., Jukkola-Vuorinen, A., Auvinen, P., Haapasaari, K., Karihtala, P. (2018) High-level cytoplasmic claudin 3 expression is an independent predictor of poor survival in triple-negative breast cancer. BMC Cancer, 18, 223. doi:10.1186/s12885-018-4141-z

High-level cytoplasmic claudin 3 expression is an independent predictor of poor survival in triple-negative breast cancer

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Author: Jääskeläinen, Anniina1,2; Soini, Ylermi2,3; Jukkola-Vuorinen, Arja1;
Organizations: 1Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
2Department of Pathology, Medical Research Center, Oulu University Hospital, Oulu, Finland
3Department of Pathology, University of Eastern Finland, Kuopio, Finland
4Department of Oncology, and Cancer Center, Kuopio University Hospital, and Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201804196713
Language: English
Published: Springer Nature, 2018
BioMed Central, 2018
Publish Date: 2018-04-19
Description:

Abstract

Background: The subtype of claudin-low breast cancer can be reliably determined only by gene-expression profiling. Attempts have been made to develop immunohistochemical surrogates, which nearly always focus on membranous claudin expression.

Methods: We assessed the immunohistochemical expression of both membranous and cytoplasmic claudins 3, 4 and 7 in a series of 197 non-metastatic breast cancers, enriched with triple-negative breast cancers (TNBCs; 60%). The expression of epithelial-to-mesenchymal transition-regulating transcription factors Sip1, Zeb1 and vimentin had previously been determined in the same material.

Results: In multivariate analysis, strong cytoplasmic claudin 3 expression was associated with poor relapse-free survival (RFS), disease-free survival, distant disease-free survival, breast cancer-specific survival and overall survival among TNBC patients (for RFS, RR 5.202, 95% CI 1.210–22.369, p = 0.027, vs. T-class, RR 0.663, 95% CI 0.168–2.623, p = 0.558, and N-class, RR 3.940, 95% CI 0.933–16.631, p = 0.062). Cytoplasmic claudin 3 expression was also associated with strong nuclear Sip1 expression (p = 0.000053), TNBC phenotype (p = 0.012) and within them, non-basal-like phenotype (p = 0.026). Cytoplasmic claudin 7 was associated with dismal RFS (RR 6.328, 95% CI 1.401–28.593, p = 0.016, vs. T-class, RR 0.692, 95% CI 0.242–1.982, p = 0.493, and N-class, RR 2.981, 95% CI 1.1016–8.749, p = 0.047). Low cytoplasmic expression of claudins 3, 4 and 7 together also predicted poor RFS (RR 6.070, 95% CI 1.347–27.363, p = 0.019, vs. T-class, RR 0.677, 95% CI 0.237–1.934, p = 0.467, and N-class, RR 3.167, 95% CI 1.079–9.290, p = 0.036).

Conclusions: Immunohistochemical expression levels of cytoplasmic claudins 3 and 7 appear to be novel prognostic factors in TNBC.

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Series: BMC cancer
ISSN: 1471-2407
ISSN-E: 1471-2407
ISSN-L: 1471-2407
Volume: 18
Article number: 223
DOI: 10.1186/s12885-018-4141-z
OADOI: https://oadoi.org/10.1186/s12885-018-4141-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: The Thelma Mäkikyrö Foundation is acknowledged for proofreading and Open Access payment.
Copyright information: © The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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