Molecular Difference between Pure Ductal Carcinoma In Situ (DCIS) and the DCIS Component of Invasive Ductal Carcinoma
Huijiao Chen, Jianmin Wang, Bing Wei, Jiping Da, David G Hicks, Ping Tang. University of Rochester Medical Center, Rochester, NY; RTI Health Solution, Research Triangle Park, NC
Background: Ductal carcinoma in situ (DCIS) is considered to be a non-obligatory precursor for invasive ductal cancer (IDC) and in all likelihood represents a heterogeneous group of lesions, with varying potential for progression. The factors underlying the evolution from DCIS to IDC are poorly understood. Here, we sought to compare a panel of biomarker expression between pure DCIS and the DCIS component of IDC in order to better define key molecular distinguishing features between these two groups.
Design: We identified 140 cases of pure DCIS between 1997 and 2008 from our departmental file, along with 212 cases of DCIS with co-existing IDC. Tissue microarrays (TMAs) were constructed for these cases. Immunohistochemical (IHC) analyses were performed on these TMAs for ER, PR, HER2, Ki-67, EGFR, CK5/6, C35, IMP3, AR and p53. ER, PR and AR were recorded as Allred scores (3 and greater as positive); HER2 was scored as CAP 2007 guidelines (>30% of tumor cells with 3+ membrane staining as positive); Ki-67 was scored as positive with >15% of nuclear staining; EGFR was designated as positive if any tumor cells showed 1+ positive stain; any strong cytoplasmic stain was considered as positive for CK5/6, C35 and IMP3; and >10% strong cytoplasmic stain was considered as positive for p53.
Results: Among the cases we were able to obtain IHC data for above molecules, we compared their IHC expression patterns between pure DCIS and the DCIS of component with co-existing IDC. We found 1) there were significant differences in the expression patterns with Ki-67 (2% in DCIS vs. 11% in DCIS component), IMP3 (1% in DCIS vs. 8% in DCIS component) and p53 (57% in DCIS vs. 39% in DCIS component) between these two groups; 2) although no difference on the expression patterns (negative, borderline and positive) was found between these two groups, the rate of HER2 over-expression was higher in pure DCIS (15% vs. 9% in DCIS component of IDC); 3) no significant difference were noted with ER, PR, EGFR, CK5/6, C35 and AR between these two groups.
Conclusions: Our data suggests that molecules including Ki-67, IMP3 and p53 may play critical roles in the progression of DCIS to IDC of breast cancer. These finding will need further validation in an independent cohort of DCIS with data of clinical outcome.
Tuesday, March 20, 2012 11:15 AM
Platform Session: Section B, Tuesday Morning