COUP TFII and Estrogen Receptor in Breast Cancer: Do They Correlate?
CA Snowden, P Kulesza. University of Alabama, Birmingham, AL
Background: COUPTFII is a chicken ovalbumin promoter transcription factor. The expression of COUPTFII is reduced in antiestrogen-resistant breast cancer cell lines. Further, re-expression of COUPTFII in resistant cells increased tamoxifen-mediated inhibition of cell proliferation, decreased motility, and increased apoptosis. These support the hypothesis that COUPTFII plays a role in antiestrogen responses in sensitive breast cancer cells and that reduced COUPTFII expression plays a role in acquired estrogen-resistance in human breast cancer. Estrogen receptor immunohistochemical staining is currently used to help determine whether breast cancer patients will benefit from antiestrogen therapy. Based on this standard, we set out to develop an immunohistochemical test for COUPTFII, to determine the levels sand patterns of expression, and to determine whether a correlation with ER expression exists.
Design: The levels of expression of COUPTFII were determined in ER negative and ER positive cell lines, in order to obtain a reference standard. Two antibodies were tested, one developed by one of the authors (CK), and the other purchased from Abcam (ab50487). A breast cancer tissue array (U.S. Biomax BR961) was stained with COUPTFII antibody (ab50487). Two independent reviewers graded the COUPTFII staining. The ER staining reported with the tissue array was used to compare with COUPTFII. A total of 86 cores, 68 malignant and 17 benign, were compared. The grading system included the intensity of staining and the percentage of cells staining (intenstity 0-3; percentage 0-100); the results were then expressed as a product of the two values (0-300). Pearson coefficient and r2 were used to evaluate correlation between ER and COUPTFII.
Results: The ab50487 antibody showed correlation between Western blotting data and Immunohistochemistry: The ER negative cell line was negative, whereas ER positive (MCF7) was positive. Average staining for COUTFII was higher in the malignant breast cases then in benign tissue. Average staining, as expected, for ER was higher in the malignant tumors than benign breast lesions. The Pearson score was 0.14 and the Rsq was 0.019. This study showed no correlation between ER and COUPTFII staining.
Conclusions: Since the low expression of ER is correlated to antiestrogen resistance, we hypothesized that COUPTFII may show co-expression patterns with ER. After developing immunostaining for COUPTFII, we detected no such correlation neither in malignant, nor benign breast tissue in this study.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 7, Wednesday Morning