Novel Technology Applied to Breast Cancer Diagnosis

A serious problem in analyzing tissue biopsies is that the tissue contains a variety of cell types, forcing laboratorians to make assumptions when interpreting data. To help eliminate these uncertainties in the testing process, a laser capture microdissection (LCM) device was developed by Arcturus Engineering, Inc. (Mountain View, CA, USA). This device enables labs to capture only the cells they need to perform genetic analyses. The new technology is being applied to breast cancer diagnosis by James L. Whittliff, Ph.D., professor of biochemistry and molecular biology at Brown Cancer Center at the University of Louisville (KY, USA). Dr. Whittliff discussed this work at the annual meeting of the American Association of Clinical Chemistry in Chicago, IL (USA). A summary follows.

Dr. Wittliff and colleagues have studied the progression of breast cancer by examining the gene expression of captured cells from the epithelium, ductal carcinoma in-situ (DCIS), and invasive ductal carcinoma (IDC) cell types taken from individual breast biopsies. So far, normal, DCIS, and IDC all have unique gene expression patterns, when expression of more than 12,000 genes was examined by microarray. The goal is to distinguish patients with DIS that are at risk of developing breast carcinoma.

A second project is a retrospective gene expression profiling breast cancer biopsies taken on average eight years ago. In this project, gene expression analysis of laser-captured IDC is being linked to pathologic, biochemical, and clinical datasets to define the molecular subtypes of breast cancer. The goal of classifying the subtypes is to identify node-negative breast cancers with a greater likelihood of early recurrence and death. Currently, there are few biochemical markers for distinguishing risk profiles, and the genomics of laser-captured cells appears promising.

Dr. Wittliff introduced the concept of a "disease quotient,” which expresses the analyte level in the diseased cells relative to that of the normal cells. Such quotients, he believes, are likely to become a revolutionary means of presenting and applying clinical chemistry results. Using LCM, Dr. Wittliff and colleagues are miniaturizing technology to measure various tumor markers in normal and cancerous cells. In this way, the level of the marker protein in the cancer cells may be expressed relative to that of the normal cells.

"The patient's normal cells serve as the reference measurement, made under the same conditions regardless of the individual's endocrine, nutritional, or aging status,” said Dr. Wittliff. He also noted that LCM is being used to recognize disease-specific proteins in order to identify potential targets for new drug development. These include estrogen and progestin receptors and epidermal growth factor (EFG) receptor.




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