%0 Generic %A L., Madaras %A N., Balint %A B., Gyorffy %A A.-M., Tokes %A I., Barshack %A A., Yosepovich %A E., Friedman %A S., Paluch-Shimon %A D., Zippel %A K., Baghy %A J., Timar %A I., Kovalszky %A J., Kulka %A A.M., Szasz %D 2016 %T Supplementary Material for: BRCA Mutation-Related and Claudin-Low Breast Cancer: Blood Relatives or Stepsisters? %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_BRCA_Mutation-Related_and_Claudin-Low_Breast_Cancer_Blood_Relatives_or_Stepsisters_/4047492 %R 10.6084/m9.figshare.4047492.v1 %2 https://karger.figshare.com/ndownloader/files/6516954 %2 https://karger.figshare.com/ndownloader/files/6516960 %2 https://karger.figshare.com/ndownloader/files/6516957 %2 https://karger.figshare.com/ndownloader/files/6516963 %2 https://karger.figshare.com/ndownloader/files/6516966 %2 https://karger.figshare.com/ndownloader/files/6516969 %2 https://karger.figshare.com/ndownloader/files/6516972 %2 https://karger.figshare.com/ndownloader/files/6516975 %K BRCA %K Breast cancer %K Claudin %K Claudin-low breast cancer %K Cell adhesion %X
Background: BRCA mutation-associated (BRCAmut) breast cancer represents a heterogeneous group displaying certain molecular features. Claudin-low breast cancers (CLBC) overlap with characteristics of BRCAmut tumors; therefore, we have investigated whether these are identical subtypes. Methods: Using public gene expression data, CLDN, CDH1, 9-cell line claudin-low predictor (9CLCLP) and PAM50 expression was evaluated in BRCAmut and BRCA wild-type (BRCAwt) breast cancer cases focusing on their possible overlap with the CLBC subtype. A separate formalin-fixed, paraffin-embedded (FFPE) cohort of 22 BRCAmut and 19 BRCAwt tumor tissues was used for immunohistochemical examination of AR, CD24, CD44, CK5/6, claudin-1, -3, -4 and -7, E-cadherin, EGFR, estrogen receptor (ER), EZH2, HER2, Ki67, p53, progesterone receptor (PgR) and vimentin expression. Results: In the data sets, CLDN1 (ROC = 0.785, p < 0.001), CDH1 (ROC = 0.785, p < 0.001), CLDN7 (ROC = 0.723, p < 0.001), CLDN3 (ROC = 0.696, p = 0.020) and CLDN4 (ROC = 0.685, p = 0.027) were expressed at higher level in BRCAmut than BRCAwt tumor tissue. The PAM50 subtype differed from the assigned immunohistochemistry (IHC)-based subtype in 30%. Based on accessible 9CLCLP predictor genes, BRCAmut breast cancer does not display the claudin-low phenotype. Utilizing FFPE samples, claudins were evidently expressed in both BRCAmut and BRCAwt cases. However, at the protein level, only claudin-3 expression was higher in BRCAmut tumors, while claudin-1, -4 and -7 and E-cadherin expression was lower compared to BRCAwt cases. A CD24low/CD44high phenotype was found in BRCAmut tumors upon comparison with BRCAwt cases (p < 0.001 and p = 0.001, respectively). Conclusions: There is a prominent correlation between the genes under focus herein and BRCA mutation status. BRCAmut tumors bear stem cell characteristics displaying a distinct cell adhesion molecule profile characterized by high expression of CDH1 and CLDN4 according to public gene expression data set analysis, and higher claudin-3 expression as detected by IHC; thus, BRCAmut breast carcinomas are not identical with the previously identified claudin-low subtype of breast cancer. %I Karger Publishers