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
|Author:||Jääskeläinen, Anniina1,2; Soini, Ylermi2,3; Jukkola-Vuorinen, Arja1;|
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
|Online Access:||PDF Full Text (PDF, 0.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201804196713
|Publish Date:|| 2018-04-19
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
The Thelma Mäkikyrö Foundation is acknowledged for proofreading and Open Access payment.
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