Basal-Like Breast Carcinoma: Identifying Estrogen Receptor Positive Cases
DC Gingell, S O'Connor, R Bhargava, DJ Dabbs. Magee-Womens Hospital of UPMC, Pittsburgh, PA
Background: Basal-like (BL) breast cancer is one of the most aggressive in terms of prognosis. BL breast cancer has been characterized on the basis of gene expression, but it is becoming common for these tumors to be defined on the basis of immunohistochemical (IHC). The triple negative (TN) phenotype lacks immunostaining for ER, PR, and HER2, and is considered a surrogate marker for BL breast cancer. Results of these immunostains are unique in driving therapeutic decisions. Sensitivity of ER antibody clones varies, and low levels of ER expression may not be detected by all clones. Given the therapeutic implications, it is important to determine if any ER clones are more sensitive for the detection of ER.
Design: The study was performed on 27 BL breast carcinoma tissue microarrays (TMAs). Each tumor was represented by 3 cores, with each core measuring 0.6mm in diameter. The BL carcinomas represented on TMA have been previously identified as triple negative tumors using 6F11 ER clone. These tumors have further been characterized by being positive for at least two of the following BL tumor markers: CK5/6, CK14, CK17 and EGFR. The tumor TMA were stained with ER clones 6F11 (Ventana Medical Systems), 1D5 (DAKO), and SP1 (Ventana Medical Systems). Whole tissue sections for 12 of the 27 TMA cases were stained using all three ER clones. H-score methodology was used to calculate scores for IHC stains. This method takes into account percentage as well as intensity of staining. The score ranges from 0-300. Any staining was considered positive.
Results: All 27 TMA cases were negative for 6F11 ER clone, where as 9 (33%) of these cases showed some reactivity using either 1D5 or SP1 clones. The average H-score for 1D5 cases was 5.2 (range 1-10); the average H-score for SP1 cases was 5.4 (range 2-10). The following table reflects the concordance between the clones:
Whole tissue sections (WTS) of 12 of the 27 TMA cases showed similar ER staining as the corresponding TMA in 6 of the 12 cases. Of the discordant cases, 4 were due to some positivity seen in the WTS whereas the TMA was negative.
Conclusions: 1) Some BL breast carcinomas, identified using IHC markers, show weak ER positivity. Using the threshold for positivity as any cells positive, these cases may not be identified as BL. 2) The number of ER+ BL cases identified is dependent upon the clone of ER used, with 1/3 of the 6F11 ER negative cases being ER+ using either 1D5 or SP1. 3) The choice of clone may fail to identify some ER+ patients who would benefit from adjuvant tamoxifen.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 30, Tuesday Afternoon