title: Claudin-3 and claudin-4: distinct prognostic significance in triple-negative and luminal breast cancer.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *1st Pathology Department §Medical School, National and Kapodistrian University of Athens †Department of Pathology ‡Breast Cancer Unit, "IASO" Women's Hospital, Athens, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Kolokytha
authors.forename: Petros
authors.initials: P
authors.lastname: Yiannou
authors.forename: Dimitris
authors.initials: D
authors.lastname: Keramopoulos
authors.forename: Argyrios
authors.initials: A
authors.lastname: Kolokythas
authors.forename: Afroditi
authors.initials: A
authors.lastname: Nonni
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Kitty
authors.initials: K
authors.lastname: Pavlakis
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000401:mortality; D062445:Claudin-1 / Q000378:metabolism; D062465:Claudin-3 / Q000378:metabolism*; D062506:Claudin-4 / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human