Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

Logullo,Angela  Flávia; Pasini,Fatima  Solange; Nonogaki,Suely; Rocha,Rafael   Malagoli; Soares,Fernando  Augusto; Brentani,Maria  Mitzi

doi:10.3892/mco.2018.1685

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

Authors:
- Angela Flávia Logullo
- Fatima Solange Pasini
- Suely Nonogaki
- Rafael Malagoli Rocha
- Fernando Augusto Soares
- Maria Mitzi Brentani
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Affiliations: Pathology Department, Federal University of São Paulo (Unifesp), São Paulo, SP 04023‑062, Brazil, Radiology and Oncology Department (LIM24), São Paulo University, School of Medicine (FMUSP), São Paulo, SP 01246‑903, Brazil, Department of Pathology, Adolfo Lutz Institute, São Paulo, SP 01246‑000, Brazil, Antonio Prudente Foundation, Hospital AC Camargo, São Paulo, SP 01509‑020, Brazil, Discipline of Pathology, Odontology School, São Paulo University (FOUSP), São Paulo, SP 05508‑000, Brazil
Published online on: July 27, 2018 https://doi.org/10.3892/mco.2018.1685
Pages: 377-388
Copyright: © Logullo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Molecular phenotyping and tissue microarray (TMA) studies have identified distinct invasive breast carcinoma subtypes: Luminal A, luminal B, enriched with overexpressed human epidermal growth factor receptor 2 (HER‑2) and triple‑negative, i.e., negative for HER‑2, as well as for estrogen and progesterone receptor (ER and PR, respectively) expression. These subtypes are useful in clinical management, since they bear distinct prognoses and predictive responses to targeted therapy. However, although molecular profiling provides important prognostic indicators, breast cancer risk stratification remains a challenge in triple‑negative cases. What is referred to as claudin‑low subtype was identified as a triple‑negative subset that is associated with more aggressive tumor behavior and worse prognosis. However, the immunohistochemical expression of claudins has not yet been standardized. Our objective was to verify whether the immunoexpression of claudins 4 and 7 (the main claudins specifically expressed in human breast tissue) in TMA is associated with survival and prognosis in luminal A, HER‑2 and triple‑negative molecular subtypes. In this diagnostic study, we investigated ER/PR receptor status, HER‑2, claudin 4 and 7 expression and stem cell CD44/24 profiles, and verified the association with prognosis and survival outcomes in 803 invasive breast carcinoma cases arranged in four TMAs. Among these, 503 (62.6%) were positive for claudin 4 and 369 (46.0%) for claudin 7. Claudin 4 exhibited the lowest expression in luminal A and triple‑negative subtypes, and the highest frequency of expression in HER‑2‑enriched subtypes, whereas claudin 7 staining was not associated with any subtype. The stem cell phenotype was not associated with subgroups or claudins 4 and 7. Claudin immunoexpression profile was not able to distinguish between patients with better or worse prognosis, and it was not correlated to triple‑negative cases. Therefore, it may be concluded that the immunoexpression of claudins 4 and 7, individually or within the usual immunohistochemical context (ER, PR and HER‑2), does not provide additional prognostic information on breast cancer subtypes.

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