Abstract
Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (well-differentiated tumors) and less favorable (poorly-differentiated tumors) outcome groups. The current system of tumor grading, however, is subjective and a large proportion of tumors are characterized as intermediate-grade tumors, making determination of optimal treatments difficult. To determine whether molecular profiles can discriminate breast disease by grade, patterns and levels of allelic imbalance (AI) at 26 chromosomal regions frequently altered in breast disease were examined in 185 laser microdissected specimens representing well-differentiated (grade 1; n = 55), moderately-differentiated (grade 2; n = 71), and poorly-differentiated (grade 3; n = 59) stage I–IV breast tumors. Overall levels of AI were significantly higher in grade 3 compared to grade 1 tumors (P < 0.05). Grades 1 and 3 showed distinct genetic profiles - grade 1 tumors were associated with large deletions of chromosome 16q22, while alterations at 9p21, 11q23, 13q14, 17p13.1 and 17q12 were characteristics of grade 3 carcinomas. In general, levels and patterns of AI in grade 2 carcinomas were intermediate between grade 1 and grade 3 tumors. Patterns of AI accurately categorized ∼70% of samples into high- or low-grade disease groups, suggesting that the majority of breast tumors have genetic profiles consistent with high- or low-grade, and that molecular signatures of breast tumors can be useful for more accurate characterization of invasive breast cancer.
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The authors thank Sue Lubert for assistance in genotyping and Dr. Michael Dunn for critical review of this manuscript.
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The opinion and assertions contained herein are the private views of the authors and are not to be construed as official or as representing the views of the Department of the Army or the Department of Defense.
This work was performed under the auspices of the Clinical Breast Care Project with funding provided by federal appropriations from the United States Department of Defense and the Henry M. Jackson Foundation for the Advancement of Military Medicine [grant MDA-905-00-1-0022 to C.D.S.]
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Ellsworth, R.E., Hooke, J.A., Love, B. et al. Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors. Breast Cancer Res Treat 107, 259–265 (2008). https://doi.org/10.1007/s10549-007-9547-2
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DOI: https://doi.org/10.1007/s10549-007-9547-2