Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype.
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.
Blanchard
Anne A
AA
Department of Pathology, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E0W3. ablanch@cc.umanitoba.ca
Skliris
George P
GP
Watson
Peter H
PH
Murphy
Leigh C
LC
Penner
Carla
C
Tomes
Ladislav
L
Young
Tamara L
TL
Leygue
Etienne
E
Myal
Yvonne
Y
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
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