Claudin-3 and claudin-4: distinct prognostic significance in triple-negative and luminal breast cancer

Appl Immunohistochem Mol Morphol. 2014;22(2):125-31. doi: 10.1097/PAI.0b013e31828d9d62.

Abstract

Introduction: To investigate the immunohistochemical expression of claudin-1, claudin-3, and claudin-4 in triple-negative breast carcinomas and compare it with several clinicopathologic parameters as well as their expression in luminal cancers.

Materials and methods: A total of 128 cases of breast carcinoma were included in the study. For all these cases, immunohistochemistry for estrogen and progesterone receptors, Ki-67, and Her2 had already been performed, whereas Her2 2+ cases had been further characterized as positive or negative for Her2 amplification with the chromogenic in situ hybridization technique. Seventy-six tumors were triple negative. The remaining 52 were luminal cancers. All tumors were evaluated for the expression of claudin-1, claudin-3, and claudin-4.

Results: In the triple-negative group, the positive expression of claudin-3 and claudin-4 was related to unfavorable and favorable prognostic factors, respectively. Claudin-1 was not related to any parameter under evaluation. In the luminal cancer group, claudin-4 positivity was related to a shorter disease-free survival, whereas the inverse was observed for claudin-3. Moreover, all 3 claudins increased with increase of the grade and Ki-67 value in the luminal cancers.

Conclusion: A distinct prognostic significance in the expression of claudin-3 and mostly of claudin-4 between triple-negative and luminal breast carcinomas was identified. Specifically, in triple-negative carcinomas, claudin-4 positivity could probably be considered as a biomarker of favorable prognosis, whereas in luminal cancers with claudin-4-positive expression, the administration of targeted therapy should eventually be part of the patients' management in the near future.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Ductal, Breast / diagnosis*
  • Carcinoma, Ductal, Breast / mortality
  • Claudin-1 / metabolism
  • Claudin-3 / metabolism*
  • Claudin-4 / metabolism*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Survival Analysis
  • Triple Negative Breast Neoplasms / diagnosis*
  • Triple Negative Breast Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2