Does Epithelial-Mesenchymal Transition Underlie Breast Cancer Metastases?
H Nassar, J Hicks, A DeMarzo, M Halushka, S Sukumar, P Argani. Johns Hopkins Medical Institute, Baltimore, MD
Background: Epithelialmesenchymal transition (EMT) is a well-recognized developmental phenomenon during which epithelial cells lose many of their basic epithelial characteristics, such as cell to cell adherence and basal-apical polarity, and acquire properties that are typical of mesenchymal cells, such as motility. In EMT, vimentin (VIM) is the predominant intermediate filament expressed, while cytokeratin expression decreases. The role of EMT in cancer metastases is highly controversial. A direct comparison of morphologic and immunohistochemical features of EMT in primary breast carcinomas and their multifocal metastases has not been performed.
Design: We performed rapid autopsies (postmortem interval, 1-4 hours) on 15 consenting patients with metastatic breast carcinoma (BC). Single-patient tissue microarrays (TMAs) were constructed from the patients' archived primary BC and multiple different metastatic BCs harvested at autopsy. TMAs were assessed for evidence of sarcomatoid morphology, which would provide evidence for EMT. TMAs were labeled by immunohistochemistry (IHC) for estrogen receptor (ER), progesterone receptor (PR), HER-2, and CK5/6 to determine the primary BC's IHC surrogate profile corresponding to breast cancer subcategories defined by gene expression profiling. TMAs were labeled for vimentin (VIM) as an immunohistochemical marker of occult EMT, and VIM expression in primary BC (145 spots from 15 cases) and matched metastatic BC (778 spots from 180 different metastatic BCs) were compared.
Results: Eight primary BCs were Luminal A (ER+, HER-2-), five were Basal-like (ER-, PR-, HER-2-, CK5/6+) and two were HER-2 positive carcinomas. Review of 778 spots from 180 MBC revealed no evidence of sarcomatoid change. All 8 Luminal A cases were VIM negative in their primary BC and all metastatic BC. 6 cases were VIM positive, including 4 of 5 Basal-like cases and 2 of 2 HER-2 positive cases. In all 6 of these cases, VIM expression was detected in the primary BC as well as the metastatic BC. Upregulation of VIM expression was noted in only a subset of metastatic BC in 3 of these 6 cases. Although VIM labeling was variable between the different metastatic BCs, a metastatic site-specific preferential increase in VIM expression was not detected.
Conclusions: Morphologically and on immunolabeling for Vimentin, established metastatic BC show little evidence of EMT. If EMT plays a major role in breast cancer metastasis, it would have to be transient and reversible.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 205, Tuesday Afternoon