The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype Export

@article{citeulike:3273682, abstract = {Summary Gene expression studies have identified a basal phenotype of breast cancer; these are hormone receptor and HER2-negative cancers with poor prognosis. High levels of cyclin E and Skp2, and low levels of p27 have previously been individually associated with both basal-like breast cancer and a poor outcome after diagnosis. The goal of this study was to first confirm the prognostic value of these biomolecular markers using a breast cancer tissue microarray. Second, we also test the hypothesis that the combined phenotype of high cyclin E, low p27, and high Skp2 would be a strong predictor of outcome and would be closely associated with the basal phenotype of breast cancer. Our cohort consisted of 438 cases of breast cancer and the median follow-up was 15.4 years. The tissue microarray was constructed from archival tumor blocks and we used commercially available antibodies for biomarker immunostaining. Cyclin E was positive in 46\% of cases, p27 was negative in 62\%, and Skp2 was positive in 35\%. We found cyclin E and Skp2 to be prognostic for breast cancer-specific survival in univariate analyses, but p27 was not prognostic. The strongest predictor of outcome was the combination of cyclin E positive and Skp2 positive (difference in survival of 19\% at 10 years, P = .0009). This combination was present in 78 (27\%) of 288 cases for which data on both biomarkers were available. This combination was also highly associated with young age at diagnosis, grade 3 tumors, ER-negative status, HER2-negative status, and the basal biomarkers epidermal growth factor receptor and cytokeratin 5/6. However, in a multivariate model including standard clinicopathologic variables, this combination was not found to have independent prognostic significance. In conclusion, the combination of high cyclin E and Skp2 expression predicts for poor prognosis in breast cancer in univariate analysis only, it is associated with high risk features, and it is associated with the basal phenotype.}, author = {Voduc, David and Nielsen, Torsten O. and Cheang, Maggie C. and Foulkes, William D.}, citeulike-article-id = {3273682}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.humpath.2008.03.004}, citeulike-linkout-1 = {http://www.sciencedirect.com/science/article/B6WGD-4SYKKT6-D/2/593191c7ccfb58bdbbccaf9af6bd7eb4}, doi = {10.1016/j.humpath.2008.03.004}, journal = {Human Pathology}, keywords = {basal, breast, cancer, cyclin-e, journal-club, pathway, phenotype, skp2, thelist}, month = {October}, number = {10}, pages = {1431--1437}, posted-at = {2008-09-16 16:36:13}, priority = {2}, title = {The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype}, url = {http://dx.doi.org/10.1016/j.humpath.2008.03.004}, volume = {39}, year = {2008} }

TY - JOUR ID - citeulike:3273682 L3 - citeulike-article-id:3273682 N2 - Summary Gene expression studies have identified a basal phenotype of breast cancer; these are hormone receptor and HER2-negative cancers with poor prognosis. High levels of cyclin E and Skp2, and low levels of p27 have previously been individually associated with both basal-like breast cancer and a poor outcome after diagnosis. The goal of this study was to first confirm the prognostic value of these biomolecular markers using a breast cancer tissue microarray. Second, we also test the hypothesis that the combined phenotype of high cyclin E, low p27, and high Skp2 would be a strong predictor of outcome and would be closely associated with the basal phenotype of breast cancer. Our cohort consisted of 438 cases of breast cancer and the median follow-up was 15.4 years. The tissue microarray was constructed from archival tumor blocks and we used commercially available antibodies for biomarker immunostaining. Cyclin E was positive in 46% of cases, p27 was negative in 62%, and Skp2 was positive in 35%. We found cyclin E and Skp2 to be prognostic for breast cancer-specific survival in univariate analyses, but p27 was not prognostic. The strongest predictor of outcome was the combination of cyclin E positive and Skp2 positive (difference in survival of 19% at 10 years, P = .0009). This combination was present in 78 (27%) of 288 cases for which data on both biomarkers were available. This combination was also highly associated with young age at diagnosis, grade 3 tumors, ER-negative status, HER2-negative status, and the basal biomarkers epidermal growth factor receptor and cytokeratin 5/6. However, in a multivariate model including standard clinicopathologic variables, this combination was not found to have independent prognostic significance. In conclusion, the combination of high cyclin E and Skp2 expression predicts for poor prognosis in breast cancer in univariate analysis only, it is associated with high risk features, and it is associated with the basal phenotype. IS - 10 JF - Human Pathology EP - 1437 TI - The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype VL - 39 SP - 1431 KW - basal KW - breast KW - cancer KW - cyclin-e KW - journal-club KW - pathway KW - phenotype KW - skp2 KW - thelist AU - Voduc, David AU - Nielsen, Torsten AU - Cheang, Maggie AU - Foulkes, William PY - 2008/10// UR - http://dx.doi.org/10.1016/j.humpath.2008.03.004 ER -