How Luminal Are Triple Negative Breast Cancers? A Cytokeratin Co-Expression Study
Gabriela M Oprea-Ilies, Yuan Liu, Dana Nickleach, Lauren A Mclendon, Stefan E Pambuccian. Emory University, Atlanta, GA; Loyola University, Maywood, IL; Winship Cancer Insitute, Atlanta, GA
Background: Triple negative breast cancers (BC)(TNT), defined by the lack of expression/amplification of ER, PR and Her2, and basal phenotype (BP) BC, defined molecularly, only partially overlap. Although BP BC frequently express “basal” cytokeratins, such as CK5, in addition to EGFR, p-cadherin and p63, while BC expressing ER, PR or Her2 (“non-TNT”) usually express “luminal” cytokeratins such as CK7, there is significant overlap in the expression of these markers. The aim of the study was to compare the frequency of "luminal" CK7 and "basal" CK5 expression in TNT and non-TNT using a dual staining approach.
Design: BC diagnosed during a 7-year period were reviewed and divided into TNT and non-TNT based on ER, PR, and Her2 expression/amplification, scored by the new CAP guidelines. Tissue microarrays were constructed with two 1 mm representative cores from each BC and were stained, using a sequential staining protocol, on a Leica Bond III staining platform using CK5 (Clone XM26, Novocastra)/brown chromogen and CK7 (CK7 Clone RN7, Novocastra)/red chromogen. This allowed the evaluation of the expression/coexpression of CK5 and CK7 in individual tumor cells.
IHC results were scored semiquantitatively, based on the percentage of tumor cells staining.
Results: 193 BC from women aged 24-90 years, 120 TNT and 73 non-TNT. were included. CK7 was expressed in the vast majority of TNT and non-TNT (91.09% vs. 84.29%, p = 0.173). CK5 was expressed in 11% of non-TNT and 59% of TNT (p<0.001) and coexpression of CK5 and CK7 was present in all of the latter. While the expression of CK7 tended to be uniform in all tumor cells, the expression of CK5 was more heterogeneous and almost all cells expressing CK5 also expressed CK7. No expression of either CK5 or CK7 was present in a minority of TNT and non-TNT (16% vs. 2%, p<0.001)
Conclusions: While "luminal" CK7 was expressed in both TNT and non-TNT, “basal” CK5 expression and CK5/CK7 co-expression was found in a significantly higher % of TNT. The fact that BC differ largely in the acquisition of "basality" and not in the loss of "luminality" suggests that they may represent a form of incomplete metaplasia, with acquisition of CK5 expression.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 3, Tuesday Morning