Phenotypic evaluation of a new molecular subtype of human invasive breast carcinoma Free

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Global gene expression profiling of human breast cancers has identified five distinct and prevalent subtypes of tumors (luminal A, luminal B, normal breast-like, HER2+/ER-, and basal-like). As a result of continuing these microarray studies we have identified a new and relatively infrequent (3-5%) human subtype that was not apparent in smaller datasets. This subtype, referred to as “Claudin-low”, is defined by the low expression of genes involved in tight junctions and cell-cell adhesion including Claudins 3,4, 7, Occludin, and E-cadherin. These tumors show a marked increased expression of B cell markers, T cell markers, and an interferon inducible signature. These tumors also showed low expression of luminal genes, inconsistent basal gene expression, and high expression of endothelial cell markers. The aim of this study was to characterize the histologic and immunophenotypic properties of “Claudin-low” tumors that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on tumors with known microarray profiles including 13 “Claudin-low” tumors and immunohistochemistry for claudin 3, e-cadherin, and factor VIII was performed. The “Claudin-low” tumors were mostly high grade ductal carcinomas with marked stromal desmoplasia. Several of these tumors showed increased tumor infiltrating lymphocytes and all but one were clinically ER-negative. Consistent with the transcriptional profiles, most claudin-low tumors showed little to no immunoreactivity for claudin 3 or e-cadherin. Additional markers and assays will be presented and these findings should facilitate further molecular, epidemiologic, and treatment studies of this rare and unique tumor subtype.