Basal-Like Ductal Carcinoma In Situ: Immunohistochemical and Morphologic Characterization
WP Devine, JT Rabban, YY Chen. UCSF, San Francisco, CA
Background: Recent gene expression profiling studies have identified a distinct basal-like breast carcinoma. The basal-like carcinoma is typically estrogen receptor (ER)/progesterone receptor (PR) and HER2 negative (triple negative), expresses basal keratins (CK5/6, CK14), and is positive for epidermal growth factor receptor (EGFR). Most significantly, this group of tumors is associated with the highest proliferation rates and the poorest clinical outcome and has been described as the prevalent subtype in BRCA1 related breast carcinomas. The precursor histologic and molecular pathway leading to basal-like carcinoma is poorly understood. The aim of this study is to characterize the immunohistochemical and morphologic profile of in situ basal-like carcinoma and contrast this with its invasive counter-part.
Design: The following triple negative cases were evaluated: 28 cases of high-grade ductal carcinoma (HGDCIS) with associated invasive ductal carcinoma (IDC) and 13 pure HGDCIS. Their pathologic features were reviewed. Biomarker expression was examined using immunostaining for CK 5/6, CK14, EGFR, Ki67, p16, Cox2, and BRCA1.
Results: Eighteen of the 28 cases (64%) of triple negative HGDCIS with associated IDC were classified as basal-like based on positive immunostaining for CK5/6, CK14, and/or EGFR. The majority of these cases (93%) had a Ki67 index >10%, 81% showed strong positive immunostaining for p16, 76% were Cox2+, and 82% were BRCA1+. The in situ and invasive components of all cases showed similar immunophenotype. Of the 13 cases of pure HGDCIS, 9 (69%) were classified as basal-like. Only 5 cases (55%) had a Ki67 index >10%, however a similar percentage of cases showed strong positive staining for p16 (67%), were Cox2+ (78%), and were BRCA1+ (75%). Most triple negative HGDCIS, regardless of basal phenotype shows solid and comedo architectural patterns (80%) and is associated with prominent periductal inflammation (60%).
Conclusions: Overall, basal-like HGDCIS and IDC show similar immunohistochemical profiles. Both demonstrate positive staining for p16 and Cox2 in the majority of cases, supporting recent reports that overexpression of p16 is characteristic of the basal-like subtype. In addition, most cases of HGDCIS and HGDCIS with IDC were BRCA1+, suggesting that while basal-like tumors are the most prevalent subtype in BRCA1 related breast carcinomas, the converse is not true. Finally, we saw a subtle but significant difference in the Ki67 index between pure HGDCIS and HGDCIS associated with IDC.
Monday, March 9, 2009 11:30 AM
Platform Session: Section B, Monday Morning