Claudin Expression in Triple Negative and ER-Positive Breast Carcinoma
Muhammad A Malik, Cynthia Cohen, Amy Adams, Jason Wang, Gabriela M Oprea. Emory University Hospital, Atlanta, GA
Background: Tight junctions play an integral role in cell homeostasis. Claudins along with occluding and junctional adhesion molecules are the main membrane proteins which form these junctions. Reduced Claudin expression may be associated with decreased cell to cell adhesion resulting in a poor prognosis in various tumors. Claudin expression has been variable in breast carcinomas according to the limited number of studies performed, including a recently described Claudin low phenotype. Here, we compare Claudins 1, 4 and 7 expression in Triple Negative breast carcinoma to that of the ER+ phenotype.
Design: Analysis was performed retrospectively on breast carcinomas using tissue microarrays of a total of 160 Triple Negative and 165 ER and/or PR+ tumors. CAP standards were used to score immunohistochemistry for hormone receptor markers ER and PR. Immunohistochemistry for Claudins 1 (1/70 polyclonal, Invitrogen), 4 (1/80 monoclonal 3E2CI, Invitrogen), and 7 (1/400 monoclonal 5D010F3, Invitrogen) was performed. Identification of positivity was based on the intensity and percent of cells staining. Cell membrane staining was considered as positive. Strong membranous staining clearly visible at 4X magnification was considered 3+, staining visible only at high power was 1+ and mid-range staining as 2+. Tumors that scored 1-3+ for intensity with 5% of tumor cells staining were considered positive.
Results: ER+ breast carcinoma more frequently showed Claudin 7 expression with greater intensity of stain and increased number of cells staining when compared with Triple Negative carcinoma(p<0.001). Claudin 1 staining intensity was greater in Triple Negative compared with ER+ breast carcinoma (p<0.001). Frequency of Claudins 1 and 4 expression, staining intensity of Claudin 4, and percent positive cells of Claudins 1 and 4 were not significantly different between Triple Negative and ER+ breast carcinoma.
Conclusions: We conclude that Claudin 7 shows a statistically significant decreased expression in Triple Negative(Claudin low) compared to ER+ breast carcinoma, portending a worse prognosis for Triple Negative carcinoma. Claudin 1 expression was differentially more intense in Triple Negative breast carcinoma. Claudin 4 expression in both populations was statistically similar.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 30, Monday Morning