Cyclin D1 and CYCLIN E Expression Analysis in Pakistani Breast Tumors Linked with BRCA1 Mutations.
Asif Loya, Muhammad U Rashid, Diana Torres, Mohammad Tehseen, Seerat Bajwa, Asim Amin, Ute Hamann. Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; Instituto de Genetica Humana, Pontificia Universidad Javeriana, Bogota, Colombia; Blumenthal Cancer Center, Carolinas Medical Center, Charlotte, NC
Background: BRCA1 and, to some extent, BRCA2-associated breast cancers have been described to have a distinct morphologic and immunohistochemical profile compared to non-BRCA1/2-associated tumors. Several biomarkers have been investigated to better characterize differences in these groups. Given the paucity of such data in the Asians, this study was conducted to investigate the expression of the cell cycle regulators cyclin E and cyclin D1 in breast tumors obtained from BRCA1/2 mutation carriers in the Pakistani population.
Design: One hundred and fifty-one families deemed to be at high risk for BRCA1/2 mutations (initial breast cancer diagnosis ≤ 30 years of age (n=84), family history of breast/ovarian cancer (n=56), male breast cancer (n=11)) were identified at the SKMCH & RC from June 2001 to November 2004. Clinical and histopathological data and blood samples for DNA isolation were obtained from all patients. Comprehensive BRCA1/2 mutation screening was performed using protein-truncation test, single-strand conformational polymorphism analysis, and denaturing high-pressure liquid chromatography analysis followed by DNA sequencing of variant signals detected by these assays (reference). Tumor tissue was available for 124 (70.4%) participants; 20 harbored a BRCA1 mutation, five had a BRCA2 mutation and 99 were negative for a BRCA1/2 mutation. Immunohistochemical expression of cyclin E and cyclin D1 was interpreted by a single pathologist, blinded to BRCA status.
Results: Breast cancer in BRCA1/2 carriers (n=25) and non-carriers (n=99) was diagnosed at a similar median age of 30 (range 22-48) and 29 years (range 22-73), respectively (p=0.37). BRCA1/2-associated breast tumors expressed cyclin E (n=20, 80%) more frequently than non-BRCA1/2 tumors (n=59, 59%; p=0.06). BRCA1/2-associated tumors had a lower frequency of cyclin D1 expression (n=13, 52%) than non-BRCA1/2 tumors (n=39, 39%; p=0.26). BRCA1-associated tumors had a significantly higher cyclin E expression (n=17, 85%; p=0.03) but lower cyclin D1 (n=12, 60%; p=0.08) expression compared to non-BRCA1/2 tumors.
Conclusions: These data suggest that differential expression of cyclin E in BRCA1-associated breast tumors may have potential to serve as a biomarker in the Pakistani population that needs to be validated in a larger study.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 23, Tuesday Afternoon