Molecular Difference between the Components of the Ductal Carcinoma In Situ and the Invasive Ductal Carcinoma (IDC), and between the Components of the IDC and the Metastasis of the Same Breast Cancer Patients
Bing Wei, Jianmin Wang, Jiping Da, Huijiao Chen, David G Hicks, Ping Tang. University of Rochester Medical Center, Rochester, NY; RTI Health Solution, Research Triangle Park, NC
Background: The key molecules involving in the progression of breast cancer from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and from IDC to metastasis are still large unknown. Here we sought to investigate the molecular difference by immunohistochemical (IHC) analysis of a panel of biomarker expression on each component for DCIS, IDC, and metastasis of the same tumor.
Design: We identified 380 infiltrating ductal carcinomas between 1997 and 2008 from our departmental file; among them, 212 cases had co-existing DCIS, and 54 cases had co-existing lymph node (LN) metastasis. Tissue microarrays (TMAs) were constructed for each components of IDC, DCIS and LN metastasis from each case. IHC analyses were performed 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; a 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 the IHC expression patterns between the DCIS and IDC components of the same case, and the IHC expression patterns between the IDC and LN metastatic omponents of the same case. We found 1) there were significant difference of expression levels for EGFR (P=0.0278), CK5/6 (P<0.0001), IMP3 (P=0.0186), AR(P=0.0348), and p53 (P<0.0001) between the DCIS and IDC components of the same tumor; 2) there was no significant difference on expression of above biomarkers between their IDC and LN metastatic components with an exception of C35 (P=0.0067).
Conclusions: During the progression of breast cancer, the accumulation of molecular alteration mostly occurs in the step from DCIS to IDC, but not in step from IDC and nodal metastasis.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 35, Tuesday Morning