Claudin-4 Expression Is Associated With Disease-Free Survival in Breast Carcinoma-in-Situ: Mean Follow-up of 8.2 Years

Clin Breast Cancer. 2018 Oct;18(5):e1111-e1116. doi: 10.1016/j.clbc.2018.06.005. Epub 2018 Jun 18.

Abstract

Introduction: Claudins are tight junctions associated with breast cancer prognosis. The claudin-low intrinsic subtype of invasive carcinoma is associated with high-grade carcinoma, low junction molecule expression, and worse response to chemotherapy. However, it is not known whether the expression of claudins may provide clues as to carcinoma-in-situ (CIS) prognosis. The aim of this study was evaluate claudin-4 expression in CIS and its association with disease-free survival and histologic type of local recurrence (in situ or invasive).

Methods: A tissue microarray block, constructed from 137 pure CIS paraffin blocks, was submitted to immunohistochemical staining for claudin-4, β-catenin, E-cadherin, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. A claudin-4 score categorized samples as claudin-4-low or -high. Clinical and treatment data were obtained from medical records.

Results: Claudin-4 expression was evaluated in 86 samples; 88.4% were high and 11.6% low. Mean follow-up was 98.4 months, and the local recurrence rate was 10.4%. There was a significant difference in disease-free survival between claudin-4-high and -low (4.9 and 1.9 years, respectively, P = .02); however, there was no difference between them in histologic type of recurrence (invasive or in situ) (P = .44).

Conclusion: In our samples, high claudin-4 expression in CIS was more frequent than low expression. Claudin-4-low expression had a worse prognosis in CIS (inferior disease-free survival), but it was similar to high claudin-4 in histologic type of local recurrence.

Keywords: Breast carcinoma; Carcinoma in situ; Claudin; Survival; Tissue microarray.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Breast Carcinoma In Situ / metabolism
  • Breast Carcinoma In Situ / mortality
  • Breast Carcinoma In Situ / pathology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Claudin-4 / biosynthesis*
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • CLDN4 protein, human
  • Claudin-4