Triple Negative Breast Cancers and Basal Immunophenotypic Expression
PH Tan, AA Thike, PY Cheok. Singapore General Hospital, Singapore, Singapore
Background: Triple negative (TN) breast cancers are aggressive tumors defined by absence of estrogen and progesterone receptor (ER,PR) and c-erbB2 expression. Between 12% to 24% of breast cancers are TN, with many expressing basal markers on immunohistochemistry. In this study, we evaluate their clinicopathologic characteristics and determine immunohistochemical expression of basal markers (CK5/6, CK14, CK17), SMA, p63, CD117 and EGFR.
Design: Archival files of the Department of Pathology, Singapore General Hospital, were searched for cases of TN breast cancers diagnosed between 2003 and 2006. Representative tumor areas were selected for tissue microarray (TMA) construction using 2 mm cores. Antibodies to CK5/6, CK14, CK17, p63, CD117 and EGFR were applied to TMA sections using the streptavidin-biotin method. Cytoplasmic staining for CK5/6, CK14, CK17, SMA, CD117; nuclear reactivity for p63 and cytoplasmic membrane positivity for EGFR were noted. Intensity (0, 1+, 2+, 3+), proportion of tumor cells stained, and intensity-percentage scores (IPS), were documented. Results were correlated with clinicopathologic parameters. A p value <0.05 defined statistical significance.
Results: Median age of 177 women with TN breast cancers was 53 years. Majority (85.3%) were Chinese, 4.5% Malay, 9% Indian, and 1.1% of other ethnic origins. Tumor size ranged from 0.5 to 20 cm (median 2.5 cm). Infiltrative ductal carcinoma was the commonest subtype (92.1%). Histologic grade 3 tumors predominated (80.8%), with grades 2 and 1 forming 11.9% and 1.7% respectively. Ductal carcinoma in situ (DCIS) was present in 45.7% of cases, and 83.9% were high nuclear grade. Node positivity occurred in 35.1%. Basal markers CK5/6, CK14 and CK17 were expressed in 16.4%, 54.2% and 80.6% respectively. SMA, CD117, p63 and EGFR were positive in 31.6%, 66.7%, 43.5% and 35% of cases. SMA intensity correlated with larger tumors and lower incidence of accompanying DCIS, while its IPS was related to the presence of lymphovascular invasion. P63 immunostaining intensity was associated with presence of DCIS. No other significant correlations were found.
Conclusions: TN breast cancers in our Asian population are high grade T2 tumors. Among basal markers, CK5/6 is the least and CK17 the most sensitive in demonstrating a basal phenotype. Our findings indicate that TN tumors cannot be directly equated with a basal phenotype. CD117 and EGFR are potential oncologic targets that may offer additional management options in this group of tumors. The presence of SMA and p63 immunostaining reflects possible myoepithelial differentiation.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 27, Tuesday Afternoon