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 approximately 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.