Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma

作者：Torsten O. Nielsen, Forrest D. Hsu, Kristin C. Jensen, Maggie C.U. Cheang, Gamze Karaca, Zhiyuan Hu, Tina Hernandez‐Boussard, Chad Livasy, Dave Cowan, Lynn G. Dressler, Lars A. Akslen, Joseph Ragaz, Allen M. Gown, C. Blake Gilks, Matt van de Rijn, Charles M. Perou · 发表于：Clinical Cancer Research · 年份：2004 · DOI：10.1158/1078-0432.ccr-04-0220 · 被引用次数：2680 · 研究领域：Breast Lesions and Carcinomas、Breast Cancer Treatment Studies、HER2/EGFR in Cancer Research

PURPOSE: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. EXPERIMENTAL DESIGN: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. RESULTS: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. CONCL...