Bruce R. Pawel, MD, and researchers at the Center for Childhood Cancer Research are creating diagnostic tools to assist in the immunohistochemical assessment of tumor tissue. Scientists are creating microarrays of small core samples (approximately 50 per slide) from tumors and from normal tissue on microscope slides so that immunohistochemical tests can be performed on large numbers of samples at once.
Modern, efficient techniques to interrogate the genetic makeup of tumors have led to the discovery of many altered genes in malignant cells, with the products of those genes having the potential to be targeted in a precise fashion for tumor treatment. The ability to demonstrate such protein expression on a cell’s surface (and not expressed in normal tissue) can be a crucial step in developing an effective and safe anti-tumor drug.
Tissue microarrays allow researchers to actually see such protein expression efficiently in a large number of similar tumors, and at the same time determine if that protein is also present in normal cells. In this way, specific biomarkers can be identified, providing information for the development of potential therapeutic targeting.
To create such a tissue microarray, needle-sized cores are taken from existing tumors and subsequently embedded in a paraffin block which can be sectioned thinly. Up to 100 tumors can thus be sampled and placed into one block, and that single tissue microarray block can be used for up to 200 experiments. Valuable and rare tumor tissue can be conserved, as the same biopsy tissue can be cored repeatedly, since the cores are so small.
Tissue microarray slides can then be sent to researchers (within CHOP and outside of CHOP) interested in the particular immunohistochemical properties of the tissue, or the immunohistochemistry can be performed in-house with the results sent to researchers who have requested assessment for specific reasons. Tissue microarrays can also be created for preclinical tissue samples.
At CHOP, many such tissue microarrays have so far been created, including for neuroblastoma, brain tumors, normal organ tissues, rhabdomyosarcoma, and pediatric embryonal tumors, and work is continuing on the development of microarrays for thyroid cancer.