Pathology - Pathology Service Staff

Sign out: Breast pathology.

Our laboratory has developed technological approaches to study gene expression in the earliest microscopic precursor lesions as well as the latest stages of human breast cancer. Specifically, we have been successful in combining laser capture microdissection, high-density cDNA array and real-time quantitative PCR (RTQ-PCR) technologies to identify novel gene expression patterns in human breast cancer. Using this approach, we have demonstrated, for the first time, that atypical intraductal hyperplasia and ductal carcinoma in situ are direct precursors to invasive ductal carcinoma. More specifically, we have shown that the various pathological stages of breast cancer progression are highly similar at the transcriptional level and that atypical intraductal hyperplasia, the earliest identifiable stage of breast cancer, is a genetically advanced lesion with an expression profile that resembles invasive breast cancer. Through bioinformatic analysis of our gene expression data, we have identified a subset of genes that correlate with both tumor grade and tumor invasiveness. We are in the process of assessing the functionality of such genes in several in vitro based assays.

In addition, we are currently focused on applying high-throughput DNA microarray technologies as a means to predict the clinical behavior of human breast cancer in the setting of specific hormonal and chemotherapeutic regimens. Recently, we identified a two-gene expression signature predictive of disease-free survival in lymph node negative breast cancer patients treated with adjuvant tamoxifen monotherapy. This two-gene expression ratio, HOXB13 compared with IL17BR, outperforms existing biomarkers in predicting outcome. Interestingly, HOXB13 demonstrates functional activity (enhances motility and invasion) in vitro and increased expression in both pre-invasive and invasive primary breast cancer. These data suggest that HOXB13 may play an important role in tamoxifen resistance and breast cancer progression, and that the HOXB13/IL17BR ratio maybe a useful biomarker clinically. We are actively studying the functional roles of HOXB13 and IL17BR as they relate to tamoxifen resistance.