title: Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype.
abstract: In the present study we investigated the protein expression of claudins 1, 3, and 4 and their relationship to clinical variables and outcome in a cohort of ER-ve and ER+ve human invasive breast cancers. Immunohistochemical analysis was performed on tissue microarrays representing a total of 412 tumors and interpretable data was derived from 314, 299, and 306 tumors for claudins 1, 3, and 4, respectively. In the ER+ve subset, 5%, 89%, and 52%, and in the ER-ve subset, 39%, 79%, and 79% of tumors stained positively for claudins 1, 3, and 4, respectively (p < 0.0001, p = 0.026, p < 0.0001). Thus, in the two subsets, a significantly higher number of tumors were positive for claudins 3 and 4, compared to claudin 1. In addition, protein expressions of claudins 1 and 4 were significantly higher in those tumors that displayed characteristics of the basal-like subtype of breast cancers (ER-ve, Her-2-ve, EGFR+ve, CK5/6+ve). This study shows a unique pattern of expression for the different claudins in ER-ve and ER+ve tumors. Our data also suggests that increased expression of claudins 1 and 4 was associated with the basal-like subtype of breast cancers, a subtype generally linked to poor outcome.
authors.affiliation: Department of Pathology, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E0W3. ablanch@cc.umanitoba.ca
authors.forename: Anne A
authors.initials: AA
authors.lastname: Blanchard
authors.forename: George P
authors.initials: GP
authors.lastname: Skliris
authors.forename: Peter H
authors.initials: PH
authors.lastname: Watson
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Murphy
authors.forename: Carla
authors.initials: C
authors.lastname: Penner
authors.forename: Ladislav
authors.initials: L
authors.lastname: Tomes
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Young
authors.forename: Etienne
authors.initials: E
authors.lastname: Leygue
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Myal
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000172:deficiency*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D008565:Membrane Proteins; D011960:Receptors, Estrogen