Yale Cancer Center/Pathology Tissue Microarray Facility

Welcome to the Yale Cancer Center/Pathology Tissue Microarray Facility, a Cancer Center shared resource. We provide the university community with services related to tissue microarray technologies. Services are also available for the biotech and pharmaceutical industries.

These services include:

  • Array design
  • Slide distribution
  • Technical support
  • Cell line and tissue controls

For information please contact the TMA Manager, Lori Charette at:
Lori.Charette@yale.edu; 203.737.4198.

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What are tissue microarrays?

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Tissue microarrays are produced by a method of re-locating tissue from conventional histologic paraffin blocks such that tissue from multiple patients or blocks can be seen on the same slide. This is done by using a needle to biopsy a standard histologic sections and placing the core into an array on a recipient paraffin block. This technique, originally described by in 1987 by Wan, Fortuna and Furmanski in Journal of Immunological Methods. They published a modification of Battifora's "sausage" block technique whereby tissue cores were placed in specific spatially fixed positions in a block. 

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Why use Tissue Microarrays?

A classic issue in biology is validation of a new concept on actual human tissue. A frequent problem is there is not enough tissue, either in amount or case number, to complete the analysis. This chronic shortage of tissue is partly due to the fact that the initial sampling is typically done by a pathologist whose primary goal is to provide a diagnostic consultation, not material for future experimentation. The difficulty of working with human tissue is further complicated by increasingly stringent guidelines regarding obtaining informed consent for its use. Thus, when tissue is obtained, it should be optimally managed to maximize its value.

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What are the Advantages?

A standard histologic section is about 3-5mm thick, with variation depending on the submitting pathologist or tech. After use for primary diagnosis, the sections can be cut 50-100 times depending on the care and skill of the sectioning technician. Thus, on average, each archived block might yield material for a maximum of 100 assays. If this same block is processed for optimal microarray construction it could routinely be needle biopsied 200-300 times or more depending on the size of the tumor in the original block (Theoretically it could be biopsied 1000's of times based on calculations of area, but empirically, 200-300 is selected as a conservative estimation) Then, once tissue microarrays are constructed, they can be judiciously sectioned in order to maximize the number of sections cut from an array. The sectioning process uses a tape-based sectioning aid (from Instrumedics Inc.) that allows cutting of thinner sections. Optimal sectioning of arrays is obtained with about 2-3 µm sections.

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Other Issues

One issue is preservation after sectioning. While the production of large batches of microarray sections is most efficient, it raises a separate problem of antigenic loss due, presumably, to tissue oxidation. While this may not be the case if you use ZN-Formalin, regular buffered formalin is more commonly used and does not prevent oxidation after sectioning. Others and we have found loss of antigenicity if sections are stored for as little as a week prior to immunostaining. Work is underway to quantify this loss. It appears that loss is an oxidative process since the loss appears to be insensitive to storage temperature or retrieval conditions.

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Automated Analysis

Quantitative expression analysis in tissue has a long and checkered history. Pathologists have devised numerous "semi-quantitative" grading systems that have waxed and waned in popularity. As the information capacity of computers increased, morphometric quantitative analysis became possible. Like the cDNA microarrays, the tissue microarray format lends itself to more quantitative analysis. However, tissue microarrays present some special problems that require dedicated readers, or at least dedicated software. An automated analysis protocol must not only be able to select the region of interest, but also normalize it so that the expression level read from any given disk can be compared with other disks. A related problem is that of subcellular localization. Comparisons of nuclear or membranous staining are quite different than total cytoplasmic staining.

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