Different Biomarkers May Play Critical Roles in Cancer Progression of Different Subgroups of Breast Carcinomas
Zhang Zhang, Jiamin Wang, Ping Tang. University of Rochester Medical Center, Rochester, NY; RTI Health Solutions, Research Triangle Park, NC
Background: Ductal carcinoma in situ (DCIS) is considered to be a non-obligatory precursor with varying potential for progression to invasive ductal cancer (IDC). The factors underlying this progression are poorly understood. We compared the expression of a panel of biomarkers between pure DCIS and the DCIS component of IDC in order to better define key molecules that distinguish these two groups of breast cancer.
Design: We identified 101 cases of pure DCIS and 225 cases of DCIS with co-existing IDC at University of Rochester Medical Center between 1997 and 2008. The clinical (patient age) and pathological (tumor size and nuclear grade) features were recorded, tissue microarray from these cases were constructed, and immunohistochemical (IHC) analyses were performed for ER, PR, AR (androgen receptor), HER2, Ki67, IMP3 (Insulin-like growth factor II mRNA-binding protein 3), Bcl2, Cox2 and Cyclin D1. ER, PR and AR were scored positive with Allred scores ≥3; HER2 was scored according to 2007 ASCO/CAP guidelines; Ki67 was scored positive with ≥15% of nuclear staining; any strong cytoplasmic staining was considered positive for IMP3; ≥10% strong nuclear staining was considered as positive for Cyclin D1, Bcl2; and ≥25% cytoplasmic stain was defined as positive for Cox2.
Results: Comparison between these two groups showed only tumor size, nuclear grade, and IMP3 with significant difference. However, when we compared different subgroups by patient age, tumor size, nuclear grade, and expression of ER/PR, HER2 and Ki67, significant difference were observed for all these factors in different subgroups. The higher expressions of ER, PR, AR, HER2, Cyclin D1 and Cox2 were associated with pure DCIS; while higher expressions of Ki67, IMP3 and Bcl2 were observed in DCIS with co-exisiting IDC.
|Age (y)||Size (cm)||Nuclear Grade||ER/PR||HER2||Ki67|
|Expression levels in DCIS > IDC|
|Expression levels in DCIS < IDC|