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Related Concept Videos

Tight Junctions01:29

Tight Junctions

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Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
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Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.

Kay Dias1,2, Anna Dvorkin-Gheva3, Robin M Hallett3

  • 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

Plos One
|January 4, 2017
PubMed
Summary
This summary is machine-generated.

Claudin-low breast cancer, a subtype identified by gene expression, can now be recognized using a specific immunohistochemical profile. This profile aids in identifying tumors associated with poorer survival but lower local recurrence rates.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunohistochemistry

Background:

  • Claudin-low breast cancer is a distinct molecular subtype associated with poor prognosis.
  • It often exhibits a triple-negative phenotype, but not all triple-negative cancers are claudin-low.
  • Accurate identification of claudin-low tumors in standard pathology samples is challenging.

Purpose of the Study:

  • To establish an immunohistochemical (IHC) profile for identifying claudin-low breast cancer.
  • To validate this IHC profile in formalin-fixed, paraffin-embedded (FFPE) tumor samples.
  • To evaluate the clinical, pathological, and survival characteristics of IHC-identified claudin-low tumors.

Main Methods:

  • Gene expression profiling was used to identify claudin-low tumors in silico (~1600 profiles).
  • Differential gene expression analysis identified candidate markers for claudin-low tumors.
  • IHC was performed on cell lines and a cohort of 942 FFPE breast cancers with long-term follow-up.

Main Results:

  • Claudin-low tumors were characterized by negativity for ER, PR, HER2, claudins 3, 4, 7, and E-cadherin.
  • IHC-identified claudin-low tumors showed associations with younger age, higher grade, larger size, and lymphocytic infiltrate.
  • These tumors had worse overall survival but a lower local recurrence rate after breast-conserving therapy.

Conclusions:

  • A limited antibody panel can effectively identify claudin-low breast cancer in FFPE tissues.
  • The IHC-based identification correlates with distinct clinical and pathological features.
  • This method provides a practical approach to studying claudin-low tumors and their clinical implications.