What's New

April 2008

CREATION OF CYSTECTOMY BLADDER CANCER PROGRESSION TISSUE MICROARRAYS

Through the use of high throughput genetic technologies, such as cDNA microarrays and serial analysis of gene expression (SAGE), numerous new markers of cancer have been identified. With the discovery of so many novel markers of disease and targets for potential therapy, there needs to be a way to quickly screen a large number of cancers for their expression of these new markers. Tissue microarray technology allows for such high-volume screening. In tissue microarrays, numerous cores (spots) of a large number of different tumors are placed into a single paraffin tissue block. This block can yield up to 300 or so slides, each containing samples of multiple (up to 300) tumors, which can be analyzed using a variety of technologies including immunohistochemistry for protein expression, in situ hybridization for RNA expression, and florescence in situ hybridization for DNA copy number. The pathology department of The Johns Hopkins Hospital has created a tissue microarray facility, which allows for construction of microarrays from tumors of any organ system. Such arrays have been constructed for prostatic, pancreatic and bile duct adenocarcinomas, and preliminary results with these arrays have shown that tissue arrays can greatly speed the analysis of new cancer markers.

We have previously completed the construction of a bladder carcinoma tissue microarray (TMA , See Figure). This microarray contains spots of 20 different bladder carcinomas, along with normal bladder specimens and normal unrelated tissues as controls. We have also constructed tissue microarrays from non-invasive papillary tumors. There is an urgent need to be able to predict which papillary tumors are destined to recur and progress, as well as to identify, which will run a benign course. Identification of benign lesions would allow the urologist to minimize follow-up, with its associated patient discomfort and expense, and to eliminate the morbidity of unnecessary therapy. In addition, the ability to identify tumors destined to progress would permit intensified surveillance and potentially early intervention therapy in order to diminish the risk of tumor death. These microarray blocks allow us to rapidly screen bladder carcinomas for novel tumor markers.

We have just completed the construction of a new set of TMAs from over 140 invasive bladder cancers obtained from cystectomy patients at Johns Hopkins University with extended well characterized clinical follow up. The case control design and the well characterized clinical data make this new TMA set of great utility to our ongoing research interest in identifying new markers that will help predict clinical outcome of invasive bladder cancer. Several exciting studies are already ongoing utilizing the new set of TMAs.