Distinct claudin expression characterizes BRCA1-related breast cancer

Marise R. Heerma van Voss, Paul J. van Diest, Yvonne H C M Smolders, Joost Bart, Elsken van der Wall, Petra van der Groep

Research output: Contribution to journalArticle

Abstract

Aims: Members of the claudin family are involved in cancer progression and are differentially expressed in subtypes of breast cancer. Breast cancers in BRCA1 germ line mutation carriers have distinct clinicopathological characteristics. Biomarkers that discriminate between BRCA1-related and sporadic breast cancer cases are needed to improve early identification of mutation carriers. In this study we evaluated protein expression of five major claudins in BRCA1-related breast cancers in comparison with sporadic controls. Methods and results: Forty breast cancers in BRCA1 mutation carriers and 40 age-matched sporadic breast cancers were immunohistochemically stained for claudins 1, 3, 4, 6 and 7. Total intratumoural expression levels were compared to those in the surrounding normal tissue. In addition, subcellular claudin expression was scored. Higher overexpression rates were observed for all five claudins in BRCA1-related breast cancers when compared to sporadic controls. In multivariate analysis, overexpression of claudin 3, 4, and 7 was mainly dependent on ER-status, whereas overexpression of claudin 6 and high membranous expression of claudin 1 were independent of other characteristics. Conclusions: BRCA1-related breast cancers are characterized by frequent overexpression of claudins. Especially claudin 1 and 6 expression may help to discriminate mutation carriers from sporadic breast cancer cases.

Original languageEnglish (US)
Pages (from-to)814-827
Number of pages14
JournalHistopathology
Volume65
Issue number6
DOIs
Publication statusPublished - Dec 1 2014
Externally publishedYes

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Keywords

  • BRCA1 protein
  • Claudins
  • Familial breast cancer

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Heerma van Voss, M. R., van Diest, P. J., Smolders, Y. H. C. M., Bart, J., van der Wall, E., & van der Groep, P. (2014). Distinct claudin expression characterizes BRCA1-related breast cancer. Histopathology, 65(6), 814-827. https://doi.org/10.1111/his.12490